Episode 13: Are GLP-1s a Miracle, a Mistake, or Something More Complicated?

In this episode, we dive into the GLP-1 conversation that’s everywhere—between “miracle drug” hype, scary side-effect stories, and the stigma that comes with seeking help. We share the kind of patient scenario we’re seeing constantly, talk about why these meds went viral, and explore what often gets lost in online discourse: nuance, individualized risk/benefit decisions, and real informed consent. We also tease what we consider when someone has health anxiety, a history of disordered eating, or is getting information (or prescriptions) through less-regulated channels. 

00:00 Podcast intro and mission
01:18 Patient story GLP-1 dilemma
03:23 Social media claims and stigma
06:29 Why GLP-1s went viral
12:06 Nugget of truth and nuance
13:51 What GLP-1 drugs are
17:57 Benefits beyond diabetes
23:57 Fatty liver and metabolism
28:37 Is weight loss a benefit
34:22 Weight Stigma in Care
35:53 When to Discuss Weight
37:46 Is Weight Loss a Benefit
39:05 BMI vs Metabolic Health
40:21 GLP-1 Weight Loss Data
43:31 Long-Term Outcomes Matter
44:53 Weight Cycling Risks
47:58 Other Potential Benefits
48:51 Common Side Effects
49:59 Muscle and Bone Loss
52:44 Cancer and Eye Concerns
56:13 Mental Health Signals
59:21 Telehealth Misuse Risks
01:02:45 Cost and Sustainability
01:05:23 Alternatives Like Metformin
01:06:29 Long-Term Treatment Reality
01:09:37 Undereating Risks
01:10:04 Early Intervention Debate
01:11:12 Biology Over Willpower
01:11:58 Environment Versus Meds
01:13:58 Weight Cycling Reality
01:15:31 Compounded GLP-1 Dangers
01:21:05 Informed Consent Lessons
01:22:42 Stigma and Patient Fears
01:27:08 Food Noise Explained
01:31:40 Fatphobia and Epigenetics
01:35:05 How We Counsel Patients
01:43:01 Resources and Disclaimer

📖 Read the full episode summary, sources, and resources on our Substack:
 👉www.theantisocialdoctors.com

Transcript

Sonia Singh MD 0:00

You are listening to the Antisocial Doctors Podcast, hosted by me, Sonia Singh, a board certified internal medicine physician with a Master's in nutrition and a special interest in health anxiety,

Rebecca Berens MD 0:10

and me, Rebecca Barons, a board certified family medicine physician with a special interest in disordered eating.

Sonia Singh MD 0:16

We're also a millennial women anxious moms and curious humans navigating social media. We've seen firsthand how these platforms can be powerful tools for education and connection, but can also make us unwell.

Rebecca Berens MD 0:28

This podcast is meant to be the antidote to your doom. Scrolling, a, solve for the anxiety, stress, guilt, shame, and confusion. That comes from social media's messaging around health. In each episode, we discuss a health related topic, trending on social media with curiosity, nuance evidence, humility, and compassion.

Sonia Singh MD 0:45

This is not your average debunking podcast. We wanna explore not just what is trending on social media, but why? Why are so many people drawn to this? What is the nugget of truth here? What are the facts? What can we learn from this as patients and doctors? No shame. No blame, no snark.

Rebecca Berens MD 1:00

We're so glad you're here.

Sonia Singh MD 1:18

Hey, Rebecca.

Rebecca Berens MD 1:19

Hey, Sonya.

Sonia Singh MD 1:21

Do you wanna start by sharing the patient story that inspired us to talk about this week's topic?

Rebecca Berens MD 1:27

Yeah, so this is a amalgamation of many patient stories, so this is not just one patient and I think there's probably a lot of my patients that will hear themselves in this story. And it's a lot of people. It's not one person. So I just wanna start right? 'cause I see this all the time. Okay. This is a patient with a history of PCOS polycystic ovarian syndrome, pre-diabetes, hyper hyperlipidemia, or high cholesterol. They've had irregular periods, they've struggled with weight their whole life. They actually developed an eating disorder as a result starting from usually around middle school on average for most of these patients when puberty starts. And as a, as as a result of that, saw multiple doctors Every time they just say, you need to lose weight. And most recently they saw a doctor that, within the first five minutes before even looking up from their laptop, recommended that they start a GLP one. And they were afraid to start it because of all the scary things that they've seen about it on social media. But they've also heard about all the potential benefits of GLP ones and they just feel really unsure and lost about what to do with this. So like I said, this is an amalgamation of multiple patients, but this is a story that I see probably almost every new patient that I see these days. Yeah this situation,

Sonia Singh MD 2:39

It's interesting because I think you have a subset of the population that's very specific and unique in that a lot of your patients have this disordered eating history. And I have a subset of the population that I think is also very unique, which is a lot of my patients have some type of health anxiety or they've had some type of medical trauma in the past. So I really feel like there's this very broad spectrum of conversations that can be had around GLP ones. There's the people who I think they might really benefit from it, but they're really nervous and they have a lot of fears, and then there's people who walk in wanting it, and that's the main thing that they want. And the main reason they're coming to see me and I'm having to think about whether it is or isn't and talk them out of it. So it's just, there's a whole there's a whole buffet of conversations that can be had around GLP one. So I'm really excited to cover this topic and kind of, get into the nuances in a little bit more detail. What do you, what would you say, I know there's probably a lot of them. What would you say is the claim around GLP ones that we're talking about today?

Rebecca Berens MD 3:29

Yeah, so I broke this down into the different categories of content I've seen and heard about from patients about GLP ones on social media. So the first one, I think this is the claim that came out like when the meds first became, came of age in early COVID when we were all on social media and worrying about our health and, wegovy was approved. So it was just basically there's this miracle drug, it's gonna end metabolic disease and obesity and save everyone, and it's the best thing ever. And it's amazing. That's the claim that you hear all the time about these drugs. And then the flip side of that is actually these drugs are terrible for you and they have horrible, scary side effects and they're the worst thing ever and no one should ever take them. There's those are the two extremes that I always see. Right. And then you have the people who are like if you're using a GLP one, you're lazy, you're cheating, you're just making yourself sicker. You just need to be, do what you should be doing. And now you're gonna be dependent on this drug. Just lots of stigmatizing and negative conversations around people who are using GLP ones. And then in the eating disorder world, actually, it's really interesting. A lot of the professionals that I'm connected with are therapists and dieticians and other physicians who treat patients with eating disorders. And there obviously when these came out was a lot of concern appropriately about the use or potential misuse of this drug when it comes to eating disorders. And also the impact that it might have on fat phobia and weight stigma. And so I think there was a very negative push against. GLP one drugs from that side of the community on social media in particular particularly when the drugs first came out. And basically saying that GLP ones are just going to worsen fat phobia and weight stigma, and they're also gonna cause more eating disorders. So that's another claim that we will get deep into in this episode. And then I think the last one, which is, this is everything, but doctors are all bought by big pharma and they're just pushing these drugs on us. And it's all a big conspiracy. So that's the other big claim. So that's the list of things that I've seen. Anything else that you've seen, Sonya, when you've, that's come up for you on your feed or your ads?

Sonia Singh MD 5:28

No, I think you pretty much covered it all. I think the thing the thing that I hear the most not just on social media, but when I'm talking to patients, is this perception that it's just a shortcut and it's taking the easy way out. And why would you put a drug in your body and, pay big pharma when you could do this thing naturally. That is the thing I hear, I would say the most often. And so yeah I'm excited to share my thoughts on that. 'cause I have plenty and I'm really curious to hear your thoughts on this idea of how GLP ones can or should or should not be used in the context of somebody with an eating disorder history. 'cause I have had a patient where she had, some eating disorder history and I did think she would benefit from a GLP one, and I felt really self-conscious doing it because I, she, we also had a nutritionist on board and I was like, is the nutritionist gonna hate me? Is the rd gonna be like this doctor? She is giving this person this drug. So I don't I'm, I remember being nervous about making that move and so I'm just curious what you think and what the data shows. Yeah. I'm excited to get into it, but

Rebecca Berens MD 6:28

yeah.

Sonia Singh MD 6:29

Tell, tell us why you think this has become so viral.

Rebecca Berens MD 6:33

So like I said, when Wegovy was approved, I think it was in 2021, so you know, this was I. Peak COVID. Yeah. We were all online all the time. And everyone was concerned about their health in a heightened way. And that's when, wegovy was first approved and came out and was, heavily promoted and discussed on social media, partially because it is truly these drugs are truly revolutionary. And I think, I don't want that to get lost in the weeds here. GLP one medications have been around, first of all, for a long time prior to 2021. Yeah. Wegovy being approved in 2021 was not the first time these medicines were used, and particularly for patients with diabetes, they have been probably the most helpful new diabetes drug that's come out in a very long time. Yeah. Made such a huge difference for patients with diabetes in particular. And so I think there was legitimate newsworthiness and press around it. But then also, if you're on a lot of image-based social media platforms and there's a drug that shows very noticeable visual weight changes, that catches attention and that did spread. And, then shortly after Wegovy came Ze and Manjaro and there was a lot of, back to back. New stuff coming out, people seeing visual representations of the effects that these drugs can have. And that got shared widely. And then I think the other interesting thing was this is when social media marketing really grew because again, during that time, when we're all on social media all of the time, 'cause we're all at home on lockdown. Social media, influencer marketing was already happening prior to that. But I think it really grew during that time out of necessity. 'cause that was the way to reach people. And in the US we've always had direct to consumer drug marketing. We can have a whole other conversation about whether that's appropriate, but that's always been happening. But now we have the added place of direct to consumer drug marketing on social media. Using images of actual people who are actually using these medications and then being paid to promote them. So just a lot of colliding things all at the same time that made this just really a big topic of conversation for everyone.

Sonia Singh MD 8:46

I think the shift of direct to consumer advertising happening on social media is something that we should all take a moment to, think about and be aware of because you and I are old enough to remember the rise of just direct to consumer advertising of pharmaceuticals. Like when all these commercials started appearing for Viagra, all of the drugs that they advertise on TV with all the actor portrayals and people frolicking through fields 'cause their knees don't hurt and all that stuff like that. That was a big shift. And then the shift now of going from those kind of generic, stale commercials to influencer marketing, being sold these drugs by people that you have a pair parasocial connection to, that you feel like and trust and that are not really beholden to some of the FTC standards that would otherwise prevent you from saying certain stuff. They're saying a testimonial, but they're also, making claims about the drug that is a very new phenomenon. And to me like that seems so much more persuasive and powerful than the commercials we're used to seeing now for the last 20 years. Yeah, that shift I think you just cannot under underestimate. But the other thing, I would say this is just me talking as a human, my memory of kind of the rise of these drugs was Ozempic was around, we were using it for diabetes. I worked with an endocrinologist. She was using it for diabetes. I remember her being like, this drug it's amazing. This is a phenomenal, like you said, it's revolutionary. Yeah. This is a shift. And she was just like this thing works so well. This is gonna replace Metformin. And I remember being like, oh wow, okay. Yeah. We're using it, my diabetic patients. And then the next thing I remember is suddenly these celebrities that had very publicly struggled with their weight for many years, who shall go unnamed, suddenly became thin, like very thin. And I feel like that was when just the pop culture zeitgeist just started to be like, whoa, what is this thing? And then for, a short period of time, it was really just a, oh, celebrities are getting this thing that's only for diabetics and they're using it to get thin. And within a matter of months it felt like it was then flooding, compounded pharmacies and patients were coming asking for it. And people were finding ways to pay cash. And it was just, it just exploded, and I think, like you said, not only in COVID did people become more aware of their health, but a lot of people became sedentary. They were drinking more, they were eating more. Not everybody, some people got more fit during the pandemic, but. I do think there was this really big, perfect storm of all of these factors happening at the same time. And it's weird and maybe it's it's just a strange analogy, but when the COVID vaccines came out, there was this very big rush of trying to get a vaccine as quickly as possible among certain segments of the population. And, wanting to get Pfizer and not wanting to get j and this, like exclusivity of in a way that medical stuff normally doesn't have. And I almost felt like when people started to become aware of GLP ones, it was a similar vibe of people coming at me all the time and being like, can you prescribe this for me? Can you get, do you have a way to get it? Do you know which pharmacies have it in stock? Do you know how I can get my insurance to come? And it's weird, but it, we had all just done this for the vaccines and now people were like, oh, this is other thing that you gotta get your hands on, so yeah, I do think there was a lot of societal, cultural, all kinds of other factors at play that ha have made this thing be such a blockbuster, but just the effectiveness alone warrants it's blockbuster status. It is a big deal legitimately.

Rebecca Berens MD 12:05

Yeah. Yeah.

Sonia Singh MD 12:06

Okay. So what would you say is the nugget of truth in some of those claims that we talked about at the top of the episode?

Rebecca Berens MD 12:12

Okay, so I think as with any medication. There are benefits and there are risks, and this is a medication, which in particular the benefits can be very great.

Sonia Singh MD 12:22

Yeah.

Rebecca Berens MD 12:22

And in some patients, the risks can also be very great. And so it is a situation that requires nuance and careful prescribing and monitoring. And I think it is true that they have very beneficial for some people. It's also true, they're very risky for other people. So we need to just be mindful of that. But it doesn't need to be all or nothing. It's not like it's the best thing ever or it's the worst thing ever. It's depends on the patient, depends on the situation and requires nuance. And we'll get into all of that with when we get into the facts. And then I think the other thing is weight stigma and bias in healthcare and in life in general is a huge problem. And I think part of what happened when these drugs came out was I remember seeing this written in several places and on social media, it was like, now there's no excuse to be fat. I've seen things, just horrible things like that, that are coming out of it. So there is a degree of these drugs are making this situation a little bit worse for people who've already been experiencing weight stigma and bias. But also they are providing a treatment option for some metabolic health conditions that we didn't really have good treatment options for before. And and so again it's a nuanced discussion and I think we're gonna get deep into the particularly eating disorder concerns around these medications. But it's a both and situation as with so many things. And so we have to be mindful and have a nuanced discussion at an individual level.

Sonia Singh MD 13:49

Yeah. Okay. Let's get into it then. Maybe we can start with just laying the groundwork of what is a GLP one drug and how does it work? What does it do in your body? Can you go over that for us?

Rebecca Berens MD 13:59

Yeah. So the GLP one stands for glucagon-like peptide one, and these are GLP one receptor agonists. It means they act like glucagon-like peptide one in the body. Okay. And as I said, these have been around for a long time. The first was approved in 2005 for diabetes, which was byta or Exenatide, and there's been several others approved since then. The first that was approved for weight loss, not for diabetes was Saxenda, which was approved in 2014. So it's not even new to have these medications be approved for patients without diabetes. Which I think is a misconception. I think a lot of people think that Wegovy was the first time that was the case, but that was not the case. And then it wasn't until 2017 Ozempic was approved for diabetes and again showed such improved glucose control and also was once a week instead of every day injections, which is huge for patients. Just in terms of patient experience of using the medication, it was an oral form of ozempic or se semaglutide was rybelsus was approved in 2019 and that also was approved for diabetes. And then in 2021 was when Wegovy injectable was approved, and that was when the tide kicked off of pursuing these medications more seriously in the general cultural context. And then an oral form of wegovy was actually approved in December of 2025. So there's also now an oral form of wa govi. And so Wegovy, Ozempic and rybelsus all are the same ingredient. They're all semaglutide or semaglutide. I don't know actually how, which way you're supposed to say. I've heard it both ways. But I think there's also a lot of confusion about what does that mean? So Semaglutide or semaglutide is the generic name for the medication that is included in Wegovy, rybelsus, and emic. They're all the same medication, just branded differently, and approved for different indications. Then in 2022, Manjaro was approved, and this was the first of its kind in approved, which is a GLP one and GIP receptor agonist. So it's a GLP one, same as Wegovy Ozempic, but also has some effect on glucose dependent insulinotropic peptide receptors as well. And so it has basically dual action. So that was approved in 2022 for diabetes as manjaro and in 2023 as Zep bound for weight loss. And so both of these medications act similarly. Again, just the the Manjaro and Zep, which the generic name is Tirzepatide are, have the dual action. But the similar downstream effects are they slow gastric emptying. So meaning it slows down the movement of food out of the stomach. It reduces glucose levels by increasing insulin secretion and decreasing glucagon. So normally when you eat and you get a surge of insulin from your pancreas, the insulin moves glucose from your bloodstream into wherever it needs to go. And then when your blood sugar is getting low you release glucagon and that takes glucose out of your tissues and puts it back into your bloodstream. And so people who are struggling with insulin resistance will have difficulty with these processes and therefore results in higher than normal glucose levels at baseline. And so that's one of the ways that this drug is helping and why it was being sought out for diabetes. They also have an impact in the brain, and this is where I think a lot of the, concern for these medications comes from because they also impact the brain in areas is associated with appetite and reward pathways. And so it can suppress appetite and it also reduces what they call hedonic eating, which I hate that term. But basically the pleasure of eating for pleasure. It reduces the pleasure feeling that you have with eating. 'cause we are supposed to feel pleasure when we eat because that is how we are driven to eat as humans. 'cause it's required for survival. And so it does decrease that. And so hopefully that was a reasonable summary of basically how these drugs are work and what they are.

Sonia Singh MD 17:39

Yeah, that's a great overview. And we have an entire episode on peptide based drugs and peptide therapeutics. And anything that ends with a tide is usually a peptide. So both tirzepatide and semaglutide are actually peptides. So keep that in mind as you navigate the world of peptides on social media as well. Okay. So can you go through what the data shows on the benefits of GLP ones and why they're so revolutionary?

Rebecca Berens MD 18:05

Yeah. I focused mainly here on the data in patients. For indications outside of diabetes, because I think For the indications for diabetes, I don't think anyone disagrees about, there doesn't seem to be controversy about that. They they work very well to control blood sugars and diabetes. I've seen such remarkable results on, for patients who were on massive doses of insulin even to control their diabetes and really struggling and just major improvements with switching or adding this medication. So I don't think that's controversial. So I didn't dig deep into that data because I didn't think that was part of the

Sonia Singh MD 18:38

I think that's

Rebecca Berens MD 18:38

fair. There's a lot to talk about. So anyway, so just to be clear, this is mostly gonna be focusing on the benefits outside of control of diabetes. So the first one I wanna talk about that I think is commonly discussed is the cardiovascular benefits. And so there are indicators that the GLP one receptor agonists separately from just controlling high blood sugar also have reduction in all cause mortality, cardiovascular mortality, and major cardiovascular events in high risk patients. And by that patients who already have diabetes or already have cardiovascular disease. So this is not in just the average person out in the world, these are people who are high risk patients. And this is coming from a systematic review and meta-analysis of almost a hundred thousand patients.

Sonia Singh MD 19:22

So it also sounds like it does not include. Just hyperlipidemia, like just high cholesterol. Is that fair? Correct. Because that is very common. And I've gotten that question before of oh, my cholesterol's high, I'm a normal-ish weight and I don't have diabetes. Should I try this?

Rebecca Berens MD 19:38

Yeah. And so I think, as we're talking through all of these studies, I think the really important thing is you have to look at who the study population is. You cannot extrapolate the results for one study population to another person who would not have fit in that study population. So as you're saying, like just plain baseline hyperlipidemia that's not cardiovascular disease, right? Yeah. So that's important distinction. So anyway, in this study, a systematic review and meta-analysis GLP ones were associated with reduced heart attack, heart failure, hospitalizations and infections compared with controls. And there was a more marked effect seen in patients who had a higher BMI. But that was, I will say that that was not necessarily one of the conditions that was required for being in the study. Some of the BA patients had BMI criteria applied, some did not. And then there was, variation noted in this study of the effectiveness and safety of various different GLP ones. Because this was not just on semaglutide or tirzepatide. This was including lide, liraglutide, exenatide, semaglutide. Okay. All the different ones. And so again, there's different efficacy and safety profiles, and so we need to tailor the drug used to the individual's risk profile and side effects and, ease of taking the medication and all of that. And so the real thing that I wanted to just be very clear about here was just having a high BMI, like A BMI above 27 plus high cholesterol, like you said, or BMI above 27 plus like none of that was the study population. So the cardiovascular risk benefits are primarily in patients who already are at high risk for cardiovascular disease, meaning they've already had some cardiovascular disease or they have diabetes. So I wanted to make that clear for this study.

Sonia Singh MD 21:24

So what you're saying is this sample included patients of a wide range of bmi? Not only patients with a certain who correct. BMI

Rebecca Berens MD 21:33

criteria. Correct. And it did not include people who had a high BMI but did not already have a high risk diagnosis. So BMI alone,

Sonia Singh MD 21:40

right.

Rebecca Berens MD 21:41

Is not the study population.

Sonia Singh MD 21:43

Okay. So for a patient who has no high risk factors that you mentioned here and is just has a BMI over 30, this does not tell us for sure whether that person is likely to have reduction of cardiovascular risk from being on these.

Rebecca Berens MD 21:58

Correct? Correct.

Sonia Singh MD 21:59

Okay, got it.

Rebecca Berens MD 22:01

The next one I wanna talk about is cardiovascular and kidney outcomes. 'cause I think this is another big discussion that happens is the benefits for not just cardiovascular disease, but also chronic kidney disease. Related to diabetes. Because that is one of the separate indications for adding a GLP one. So if you have a patient, for example, who has diabetes and it's well controlled, but they're not on a GLP one, it, it's actually maybe worth switching them because of this potential kidney benefit. And so this was a systematic review and meta-analysis of randomized placebo controlled cardiovascular and kidney outcomes trials. And it was looking across 10 trials and the long acting. This was specifically the long acting GLP ones. So that's like the, semaglutide and tirzepatide reduced the incidence of major adverse cardiovascular events. So that's things like heart attacks and and like serious heart heart outcomes and the composite kidney outcome and all cause mortality. And there was consistent 14% reduction for all of these components. And there was no significant difference whether it was given by injection versus orally.

Sonia Singh MD 23:07

Okay.

Rebecca Berens MD 23:09

And again, these are all in patients with diabetes. So to be clear, this is not just random patients with A BMI over 30 or patients who don't have diabetes. This is only for patients with diabetes, but for patients with diabetes, there is an a reduction in both cardiovascular and kidney outcomes with these medications.

Sonia Singh MD 23:25

Okay.

Rebecca Berens MD 23:26

I don't wanna get too into the side effects part yet, but one thing I commonly hear about is concern about kidney problems with these medications. And yet we are also using these medications to help with kidney benefits. So that can be confusing for people. And I think the important thing there is a lot of times when there's kidney problems associated with these medications, it's usually acute kidney injury related to dehydration. Yeah. If the patient is not intaking enough fluid or is having diarrhea as a side effect. So we'll get more into side effects later, but just to be clear, these are different things that we're talking about? Yes,

Sonia Singh MD 23:56

Yes.

Rebecca Berens MD 23:57

So the next benefit that I wanna talk about is metabolic associated STO liver disease or metabolic associated s STO hepatitis. And so this means basically fatty liver is the colloquial name for this condition. And so you can have excessive fat deposits in the liver that are just there, and then you can have excessive fat deposits in the liver that are causing inflammation that can then progress to scarring, which can progress to cirrhosis. So this is a significant condition.

Sonia Singh MD 24:24

Is this the new name for non-alcoholic s hepatitis?

Rebecca Berens MD 24:28

Is

Sonia Singh MD 24:28

this under that umbrella?

Rebecca Berens MD 24:29

Yes, this is the new name for non-alcoholic Seattle

Sonia Singh MD 24:31

Hepatitis. Okay. You're teaching me something new. Thank you for the, thank you for the CME.

Rebecca Berens MD 24:35

Yeah, no worries. Yeah. For the patients out there, I think a lot of people are now familiar with the term fatty liver. Fatty

Sonia Singh MD 24:40

liver. Yeah.

Rebecca Berens MD 24:40

And and fatty liver is associated with metabolic health conditions, particularly insulin resistance. It results in excessive fat deposits in the liver. And like I said, as they continue to be there and are and grow, they can cause inflammation and they can eventually progress to cirrhosis. So this is a serious condition and something that deserves attention because cirrhosis, is liver failure and results in the need for transplantation in some cases. And so it's a serious condition that's worth

Sonia Singh MD 25:07

and

Rebecca Berens MD 25:07

it's fairly

Sonia Singh MD 25:07

common.

Rebecca Berens MD 25:08

Very common. And I actually think more common, I have a whole soap book about this that we can go off on, on another day. But I actually think dieting is a big reason that we have a lot of this nowadays compared to before. Oh, that's

Sonia Singh MD 25:18

fascinating. I definitely wanna hear more about that.

Rebecca Berens MD 25:20

We need to put a pin in that and we'll have a whole other. Oh my gosh. I didn't, why? I think chronic diet causes metabolic associated fatty liver, but anyway, so this study was looking at GLP ones for. Specifically this indication, metabolic associated steato liver disease or steato hepatitis. And this included 25 RCTs or randomized controlled trials. And it included liraglutide, exenatide dulaglutide, semaglutide, tirzepatide, and I can't even pronounce those other two but anyway and there was GLP ones were given for a median of 24 weeks and demonstrated a significant reduction in liver fibrosis by 5.21%. ACHI tried, which is not yet approved in the US was one of the ones also included in the study, and that had the most significant effect. And it induced significant histological improvements, meaning like looking under the microscope at tissue, there was actual improvement in how the tissue appeared. Hepatocellular ballooning and lobular inflammation, but not significantly improved fibrosis with the evidence for tirzepatide more robust than that for semaglutide and liraglutide. It also significantly decreased liver enzymes including A-S-T-A-L-T and GGT compared with the control. It improved liver stiffness and there were no adverse effects of adverse effects involving the liver observed. All that to say there is benefit for patients who have steatohepatitis using these medications. But again, this is not just any random person who has. A high BMI, this is just people who specifically have this condition that are benefiting from,

Sonia Singh MD 26:54

This kind of makes sense in part because I'm curious what the BMI of these patients were and what weight loss outcomes they had. Because one of the primary treatments, at least that I know of for Seattle Hepatitis is weight loss. And so if these drugs helped them achieve that it would make sense that they then had, histologic changes that moved them in the right direction. Okay.

Rebecca Berens MD 27:16

So yeah. So fat loss from the liver. Yes. Yes. I, and I think this is where my whole soapbox comes from. If you lose weight, gain weight, lose weight, gain weight, every time you do that, there's actually more fat gained in the liver. Because the way that your metabolism shifts with recurrent loss in gain uhhuh, there it is actually that's why I personally don't feel that weight loss as a treatment is a beneficial recommendation because weight loss is often not sustainable. I think the sustainable changes that we can make metabolically, like increasing fiber and exercising and, using medications when indicated can all be helpful. But I think it's more so at a metabolic level affecting the liver than it is just dropping weight. Because I always say this too, you could you could go get liposuction and you would lose some weight. But that wouldn't change your metabolic outcome. So it's not the weight that's the problem. It's the how you lost the weight. And so how you lost the weight. It has more to do with your behaviors than it has to do with the actual pounds lost.

Sonia Singh MD 28:17

Interesting. Okay. I am not familiar with all the deep data on this, so I will have to

Rebecca Berens MD 28:23

reserve judgment.

Sonia Singh MD 28:23

We

Rebecca Berens MD 28:23

have to we need to do another episode just

Sonia Singh MD 28:25

on Okay. We'll do another just

Rebecca Berens MD 28:25

on national fatty liver.

Sonia Singh MD 28:27

There's a lot of crazy stuff about fatty liver on, on social media too. Yeah. There's a few people that have made a buck or two with some fatty liver miracle treatments. Okay. Okay. So now tell us about the grand finale Weight loss. Okay. Tell us about weight loss.

Rebecca Berens MD 28:41

Okay, so weight loss. Is this a benefit? I don't know. I

Sonia Singh MD 28:46

Oh, interesting take you're starting with. Okay. Yeah.

Rebecca Berens MD 28:48

Yeah. I think, so where we're talk, because we were talking about all the benefits, right? What is the benefit of weight loss? And I think this is where it gets sticky because all weight loss is not good, and I think there often in medical community is this sort of oh, you lost weight. That's great. But it could actually be for a really bad reason. And and for people whose starting weight is lower, when they lose weight, they're approached with concern and evaluation and with people whose starting weight is higher and they lose weight, they're congratulated, even if the same condition caused the weight loss in both people, right? And I think it's important to I, I don't feel that looking at weight loss specifically as a benefit is helpful because it doesn't directly map to improved health outcomes. It's just a change in body weight. Now, I think there are people who are struggling with mobility related issues that certainly can benefit when they lose weight. Like maybe they're less pressure on arthritic joints or things that makes it easier for 'em to move around. There are things where the actual body weight change makes a difference. But in terms of the actual health outcomes, I'm not so convinced that always has such a huge benefit. But anyway, we'll get into the

Sonia Singh MD 30:02

data here. So always I'm gonna push, I'm gonna push back on you here a little bit because always is a hard thing to say, right? But. I have had many patients who, like I have a lady who was on three different blood pressure medicines and I had her for years and years, and we were always trying to get her blood pressure under control and now she's lost like 25 pounds with the GLP one and she's on zero blood pressure medicines. And that is not the case for everybody. Plenty of people will still have to be on their blood pressure medicine and that will not change. And she also had high cholesterol and that did not change even with weight loss. But now she feels more confident and comfortable taking the med I've given her for her high cholesterol because she understands, even when she is really following a very a HA appropriate kind of heart healthy diet, even when she does that, the cholesterol does not change. And even when her weight doesn't under control, the cholesterol does not change. But, so yeah, that will not be the case for everybody. But, sleep apnea, sleep ap, a lot of people no longer have sleep apnea after they have a significant weight loss. So I guess to me, I think the, I'm not saying that weight loss always in and of itself is good. There's certainly a way to lose weight in a very unhealthy way with or without GLP ones. But I think there are many benefits potentially beyond just the number changing on the scale or cosmetics or, whatever.

Rebecca Berens MD 31:22

Yeah, I think Okay. Blood pressure, for example, like yes, if you are at a higher body weight, the blood pressure generally does increase because there Yeah. It's a physical change. I think high blood pressure, like I, I have a lot of patients who their BMI is in the overweight or obese category based on, the current guidelines around BMI who do not have high blood pressure Yeah. Who are metabolically very healthy, who follow good behaviors, but still would qualify by FDA approval to use one of these medications. And I guess that's what I mean when I say is that really a benefit? Because what, what are we treating? We're, are we treating the weight or are we treating the metabolic problems? And I think that's why I get caught up in this because I feel that if someone has high blood pressure and high cholesterol, like your patient that you're describing They have a metabolic health issue that's causing that to be the case, right? Yes. And so if we treat that issue and those conditions improve, that's great. All, all good. But if I have a patient who's otherwise doing really well but just their BMI is high, I, I struggle with the. The ethics and the discussion about why would we medicate that? And so that's the reason I say like, why is that a benefit? And I think to me it's more so what are the actual observable metabolic health outcomes that matter. And I don't see just weight loss as an outcome that actually matters.

Sonia Singh MD 32:54

Okay. I see where you're coming from by saying in those cases where people are having benefit, it is not necessarily the weight that is the benefit. It is the treatment of an underlying metabolic disorder or pathology, that is what's giving them the benefit. I think, no, no one is telling you that this has to be given. I would not if A 30 if a person with A BMI of 30 walked in and or 35 and was like, I'm comfortable at the weight I'm at, I feel good. I do what I wanna do. I get around, I don't have any issues with it. And they had no, other medical conditions that seemed to be. Exacerbated by their weight alone. I certainly would not be like you should be on this,

Rebecca Berens MD 33:38

you wouldn't Sonia, but many doctors would.

Sonia Singh MD 33:42

Yes, okay. But I could also have somebody who was exactly like that same stats, same figures who says to me, yeah, it's not really getting in the way, it's not really interfering with my life, but I feel uncomfortable in this body. And I would really like to lose 20 pounds. And I've been trying to do it every other way and I just haven't been able to. And in that person I would absolutely talk to them about it. And that would be just the benefit of weight loss. But tell me what your thoughts on that would be.

Rebecca Berens MD 34:11

Yeah, I think that's tricky because if they're not having any health problems and they're moving around and they're able to do all the things they wanna do, why is it that they're uncomfortable in their body? They're uncomfortable in their body because of societal stigma tells them

Sonia Singh MD 34:26

well,

Rebecca Berens MD 34:27

I do. So that's a problematic issue, and so I think the, like what you said, if this patient comes into your office and they're not worried about anything, you're not gonna push a GLP one on them. Yeah.

Sonia Singh MD 34:38

Right.

Rebecca Berens MD 34:38

A lot of doctors would, and that would happen, right? Lot of times these patients might come in for I, I've had patients tell me they went in for an ear infection and we're told to lose weight. I've had patients who were at an exercise class exercising yes. And sustained an injury doing that exercise, then went to the doctor to get treated for it, and were told, oh, you just need to lose weight. And it's I was literally exercising.

Sonia Singh MD 35:03

Yes.

Rebecca Berens MD 35:03

So that constant barrage of nagging is that, is creating discomfort and is also affecting the quality of their healthcare for no good reason.

Sonia Singh MD 35:15

Yes, and I'm not, I am not denying at all that weight stigma exists. It for sure does. And I'm also acknowledging that probably my practice differs slightly. Like I don't even really have the weight conversation with somebody unless they bring it up. Or it comes up in some other way, I don't independently just say let's talk about your weight. I just never do that. I don't even, I ask people if they want to be weighed, yeah. So it, this is a very, I understand that is not typical of traditional medicine, so I can see what you're saying, but I think that's more it's more of a societal and cultural critique than it is necessarily about this drug specifically. So going back to that same patient is a patient had BMI of 30, otherwise healthy, no other metabolic issues that we know of isn't held back a lot. And I've had this conversation so many times with people. So a lot of times in that case I'll say, okay, tell me a little bit more about what your goal is. What is the intention here? What is the goal? Where do you wanna get to and why? Because I don't care about trying to get people to certain BMI and if we're just on it to be on it and lose some weight let's talk about why and what, where we're gonna stop and how this is gonna go. And a lot of times what they'll tell me is I'm worried that I'm okay now, but what if this continues and I just get larger and then I start having those problems. I don't wanna wait until I do have sleep apnea. I don't wanna wait until my knees do start hurting. If there's anything I can do to lower my cardiovascular risk long term, like I wanna do it now. Those are the kinds of things that people often say in response when I'm just okay, tell me like what the motivation is, sure. And sometimes it is just, I wanna feel better in my clothes. I don't feel like anything fits me right anymore since I've been at this suite. I just want, then it becomes that, which I hear what you're saying in that. If somebody who. Had a normal BMI said that to me. I may be more, moving towards acceptance of our money and yeah, medically this is not a problem. And you, and maybe when someone with a BMI of 30 says that to me, I'm a little bit more open to say there are interventions or there are things we can do to help you. So I can see, I can hear what you're saying that like, why would I say that to somebody who is of a quote, normal weight. Whereas I would not say that to somebody who's, but again, I would say that is because I think there is an argument to be made that perhaps down the road that weight could present a problem for them. And maybe if they're driving it too, then I can be on board with that. So I don't know. You I'm telling you what I think a lot of people are. Yeah. Hear what you're saying and say to you.

Rebecca Berens MD 37:46

And I hear you and I, my answer to that would be the benefits and the risks for you at this moment. What do we have on the benefits and risks for you at this moment? Weight loss alone is the only benefit that we have right now. If we don't have any other metabolic issues going on, right? Sure. If you have fatty liver, if you have high sleep apnea, these other things going on, that's a different conversation. But if we have no other issues. And it's just weight loss, is that a sufficient benefit to outweigh all the potential risks that we're gonna talk about? And so that's just the framing that I wanna approach this with because I struggle with that as a benefit for no medical reason. And again, if there's medical, other things going on, it's different. But if it's just the way, if you said it was just, I wanna fit in my clothes better I think it is very interesting that we would have a different approach to someone with a quote, normal BMI versus someone with a quote, hi BMI, saying that same sentence. And I think that is just something that we all should self-reflect on why that is the case, because we all know that BMI is an extremely flawed metric that is based on white men in Belgium and not the diverse women that live in the US today. So that's my, okay. We'll

Sonia Singh MD 39:05

take into account all the flaws within the actual metric of the BMI, what about various conditions for which obesity has been identified as a risk factor?

Rebecca Berens MD 39:18

So I, I think the issue in that, in most of those cases is related to metabolic dysfunction, hyperinsulinism.

Sonia Singh MD 39:25

Okay. So you're saying in order to really get to the bottom of that, you would have to distinguish. Patients who meet certain BMI criteria who have metabolic dysfunction versus patients who meet the same criteria but have no metabolic dysfunction and then redo the study to see Yes. If it's still associated with it.

Rebecca Berens MD 39:45

Yeah. And I feel like that, ha, that's never done. 'cause everyone just lumps them together. And I don't think it's fair to do that. And there's also people who have a quote, normal BMI, who have metabolic dysfunction.

Sonia Singh MD 39:55

Of course,

Rebecca Berens MD 39:55

yes. Yes. And so I just think it's, it is a it is a bias that exists for many years in our medical literature and in our, in the way that we approach patients. And I think it is something that we should all reflect on. And I, that is why I say I'm not sure that I count weight loss as a benefit, but for the purposes of the studies I'm about to talk about, this was the outcome measure that was measured as a benefit.

Sonia Singh MD 40:17

Okay.

Rebecca Berens MD 40:18

That's what we're gonna go,

Sonia Singh MD 40:19

I'm gonna let you move on. Okay. Tell us about weight loss. Okay.

Rebecca Berens MD 40:23

So

Sonia Singh MD 40:24

I say quote unquote benefits,

Rebecca Berens MD 40:26

Quote unquote. Okay. This study efficacy and safety of glucagon light peptide receptor agonists for weight loss among adults without diabetes. Okay. So this is the big systematic review. So this is reviewing a total of 26 randomized controlled trials over 15,000 participants. And it included 12 agents, three commercially available agents, and nine pre-market agents. Treatment ranged from 16 to 104 weeks with a median of 43 weeks. So that's less than a year also, which is important to know. Tirzepatide, liraglutide RERA tach ide and semaglutide all resulted in weight loss. Tirzepatide was up to 17.8%, semaglutide 13.9%, liraglutide 5.8%, and reride 24.9% after 48 weeks. And so there were varying degrees of efficacy, but all resulted in significant weight loss. Adverse effects were frequent, but the majority of which were GI related, nausea, vomiting, diarrhea, and constipation. But. Adverse effects that were severe enough to actually stop taking the medication. Were pretty rare. And

Sonia Singh MD 41:36

so

Rebecca Berens MD 41:37

that and

Sonia Singh MD 41:37

serious adverse events were even rarer

Rebecca Berens MD 41:39

Yeah. Yeah. As, yeah. Severe adverse events were even, were also rare.

Sonia Singh MD 41:43

24.9% weight loss is insane. That is a lot of ways.

Rebecca Berens MD 41:47

And so that's also my question is like, where is our line? What is our goal? Because I think a lot of people look at these studies and they're like, oh it makes you look great. I'm like, yeah, but that's not universally good. And there's at what point do we decide it's enough?

Sonia Singh MD 42:02

Yeah. And I just wanna point out that, these are not the first weight loss drugs. There were weight loss drugs before this, there was fenden, many people will remember. Phentermine was one of those ingredients. There's orlistat, Lorrin Vic. There, Contrave, there were drugs before this, but nothing with this level of effectiveness. Yes. And tolerability. So this really is quite an advancement in this, category.

Rebecca Berens MD 42:28

Yeah. And a lots of those things were later pulled.

Sonia Singh MD 42:31

Yes. They were.

Rebecca Berens MD 42:33

So

Sonia Singh MD 42:33

none of them were great. Hated all of them actually.

Rebecca Berens MD 42:35

Yeah. So the thing is I think. There is weight loss with these medications, but I think we just have to assess what is the actual benefit of that. Okay. So then this one here this one is the an original WEGOVY trial. So funded by Novo Nordisk once weekly semaglutide in adults with overweight or obesity. And this is looking at the primary endpoints of weight loss. It also looked at waist circumference change, systolic blood pressure, physical functioning score. So this has actually some more endpoints that are not just related to actual weight loss, but also medical and lifestyle related endpoints, which are lowering of blood pressure and physical functioning improvement. So I think that is a little bit more relevant. Yeah. There was less significant change in things like lipids and inflammatory markers and A1C and things like that, but at least there are some medical markers that have some evidence of significant changes. And then for Tirzepatide,, there is a meta-analysis of nine randomized controlled trials containing over 7,000 participants. They're mainly for middle and high co countries. The main comparison was tirzepatide versus placebo. But there was one that was Tirzepatide versus Semaglutide. And it did include participants who had other medical comorbidities, not just high BMI. And these included both medium term follow ups, most of them, which was about 12 to 18 months. And one was long-term follow up at 3.5 years. And there was evidence of weight loss at medium term followup and sustained weight loss at the longer term followup. But there was less indication of long-term impact of other patient important outcomes like quality of life mortality, major adverse cardiovascular events, all of those things. And again, this did include patients who had other risk factors, not just. High BMI. So the major adverse cardiovascular events, if there was any impact on that is, is not as applicable to someone who doesn't have those other risk factors.

Speaker 3 44:30

Right.

Rebecca Berens MD 44:31

And so the reason I say all of that is it's important one, that we're not just looking at weight loss as an outcome, but we're looking at actual medically and patient important benefits. And that we are seeing sustained benefit because we do have evidence that not sustaining weight loss without sustaining it, is actually very harmful. So there was a really interesting study done at Vanderbilt in published in 2025, is called weight trajectory impacts risk for 10 distinct medi cardiometabolic diseases And compared to weight stability, weight cycling associated and almost 30% increased risk for obstructive sleep apnea, metabolic dysfunction associated sto, liver disease type two diabetes, and an 50% in increased risk for heart failure. And so basically comparing someone who lose gain, versus someone who just stays at the high BMI, even if those BMIs are the same. You actually do worse metabolically when you cycle than if you just stay there. Yeah. And that's what I think is really important and I think is not discussed enough. Because if we're gonna put someone on a medication like this is considered to be a lifelong medication. Yeah. If we're treating you for something that we have identified to be a metabolic condition, we don't expect it's gonna go away on its own. And so if you're gonna be treated for it, you're gonna be treated for it lifelong. And so if you cannot sustain the treatment and you lose gain, 'cause you're coming on and off, you actually may have worse outcomes than if we just left you alone. And that's the reason that I, particularly for people who don't have other risk factors, think it's very important that we think very clearly about what is the actual benefit for this patient versus the risk. And this is a risk that I think is not discussed enough.

Sonia Singh MD 46:17

Yeah. This study, I've looked at this study before and to me, this answers the question I get from so many of my patients who are women in their fifties who have been dieting their entire life and they've just been gaining and losing the same 25 pounds for like decades and decades. And then they come to me and they're like in their mid fifties and they're like, I don't know, I'm only eating 800 calories. And nothing is happening. Like literally I've had people tell me I'm only eating 800 calories and I don't lose any weight. How can, how is that physiologically possible? And I really think it's this effect of cycling leading to this high degree of metabolic dysfunction that then just, it's, it creates an even steeper hill for them to try to climb if they're trying to lose anything. And. They're not healthy, yes. In any way. And yeah, I'm glad that you brought this up in this context and, I think a lot of people do have this question about, what's the long term plan with this? That's one of the most common questions I get from patients. Another common question I get, which I don't think is really answered by any of the research is what is really the ideal pace of weight loss? We can see in the studies what happened to people, but protocol was, is just keep ramping it up until they do not tolerate it anymore, or they get to their goal weight. And I don't know that we've really just is we have not proven or determined if there is an ideal rate that we should bring people down. Because a big concern with this, and we talk about this in our protein episode, is sarcopenia, anytime you have massive weight loss, you can also lose muscle mass. And we know that there's a lot of downstream bad health consequences of losing too much muscle mass and having sarcopenia. Yeah. Anyway, all, all important points that we need to talk about.

Rebecca Berens MD 47:57

Yeah. And then the last potential benefit that I'm gonna mention, and this is still early. There is some animal and very early observational human data of reduced substance use behaviors with GLP ones. And there's also a lot of study around other psychiatric conditions as well because again, this is a medication that is impacting the brain and is involved in reward pathways. And so it makes sense that there would be some interaction with substance use and potentially some other mental health conditions. But this needs a lot more further study. This is not something where we're like ready to claim anything about, clear benefits with the GLP ones for

Sonia Singh MD 48:34

research. So as of now, the FDA approved indications are really diabetes, obesity, and sleep apnea are the ones that I think are official.

Rebecca Berens MD 48:44

Yeah. And then and fatty liver disease and kidney disease, but again, in people with diabetes,

Sonia Singh MD 48:48

in people with diabetes. Yeah. Okay. Yeah. Okay. Okay, so now let's talk a little bit more about risks and side effects.

Rebecca Berens MD 48:55

Yeah. Most common and clearly documented and definitely these are real side effects is GI side effects. And the most common ones are mild. So like nausea, upset, stomach, heartburn, constipation, sometimes diarrhea, usually mild. Usually adjust within a couple of weeks and then diminish over time. And then become more tolerable. Gallbladder events, meaning like gallstones and and biliary colic that that can be increased also. And that could be potentially more serious because gallstones can cause pancreatitis, in some cases they can cause infections. There, there can be more serious side effects, related to gallstones, but those are also less common. And these are dose dependent side effects. So there was a meta-analysis that showed a increase of 26% in gallbladder disorders with GLP one receptor agonists, so Relative risk increase, but again, still not super common. And the most common ones are those more mild and adjustable yeah, side effects. And then as you mentioned, the loss of lean mass is another big concern that people have with side effects. And there was a study that showed it said nutritional priorities to support GLP one therapy for obesity at joint advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and the Obesity Society. And they have guidelines about how to reviewing a variety of studies and how to minimize this effect on sarcopenia. And what they have found in various studies is that the amount of lean mass loss is comparable to, or less than that abor observed with bariatric surgery and very low calorie diets, which is s significant. Yeah. But exercise is something that can mitigate some of that risk. So there was a secondary analysis of a randomized clinical trial called bone health after exercise alone, GLP one receptor agonist treatment or combination treatment. And so this study, I thought was horrible in terms of to be a person in this study an eight week low calorie diet of 800 calories a day. Ooh. Yeah.

Sonia Singh MD 51:02

Real low. Okay.

Rebecca Berens MD 51:03

Horrible. Participants were randomized to one of four groups for 52 weeks, and so they all did the 800 calorie calories a day diet. And then they went to one of four groups. So either a moderate to vigorous intensity exercise program alone, a GLP one alone, or the combination of a GLP one plus exercise or placebo. So all did 800. And did

Sonia Singh MD 51:24

they continue the 800 calorie diet? No. Oh, okay.

Rebecca Berens MD 51:27

Okay. Yeah. So they all did the 800 hundred calorie diet in initially, and then they all went to these other forearms.

Sonia Singh MD 51:34

Okay.

Rebecca Berens MD 51:34

And they all did of course have lean mass loss. But in the combination group, meaning GLP one plus exercise, the bone mineral density was unchanged with placebo at the hip and lumbar spine. So not being on a GLP one or doing or doing any exercise like placebo had the same bone density as being on a GLP one and doing exercise.

Sonia Singh MD 51:59

So basically the idea is that as long as you're doing exercise with the GLP one, it cancels out Yes. Perhaps the bone density loss

Rebecca Berens MD 52:07

that it has. Because if you did, if you were in the exercise group, meaning no GLP one versus the GLP one group the exercise group had better bone mineral density than the GLP one group.

Sonia Singh MD 52:18

Right.

Rebecca Berens MD 52:18

So these

Sonia Singh MD 52:18

effect the law, the effect on bone loss can be mitigated somewhat with exercise.

Rebecca Berens MD 52:22

Yes.

Sonia Singh MD 52:22

I heard this a lot, this critique a lot in the early days of GLP ones, even from other doctors where they'd be like, oh, that's just so horrible. Everyone's just gonna lose all this muscle mass. And I think it's true and these studies seem to support that, that, any weight loss of that magnitude will make you lose muscle mass. It's gotta be done with, the exercise or weight training piece of it in order to maintain that and the bone density. Yeah. Okay. Go on.

Rebecca Berens MD 52:44

And then a couple other side effects that I hear a lot about that are actually less concerning than people worry about. So one is I think people have heard a lot about these eye side effects. Yeah. And so this is actually primarily in people who have diabetes and have preexisting retinopathy or retinal blood vessel disease. If we rapidly lower their blood sugar with anything, not just a GLP one, but with any other medication, they also can have this same effect. So this is more of an effect of the rapid lowering of blood. Yeah. Sugar affecting the retinopathy than it is a direct effect of the drug. So less of a concern than I think it is made out to be. The other one is cancer risk. So there, there is this black box warning about thyroid cancer and that if you have this specific multiple endocrine neoplasia type two family history or personal history that is a contraindication. You cannot use this medication. This is based on some, in some animal studies where in rodents there was a risk for inducing C cell tumors in the thyroid. But it's questionable that this would happen in humans because the levels of GLP one receptors in rodents are very different than they are in primates or humans. And and they were also using much higher doses in rodents. So we don't think this risk really applies that much to to humans. And actually there was a study where they looked at this because you also mentioned earlier about the o the other, like obesity associated cancers, for example.

54:07

Yeah.

Rebecca Berens MD 54:07

And there was a study looking at cancers in general GLP one receptor agonists and cancer risk in adults with obesity. And it compared the incidence of 14 cancers among adults with obesity prescribed GLP ones versus non-users. It was a retrospective cohort study and it was using EHR data from 2014 to 2024. And the primary outcomes were the incidence of 14 cancer types, including liver, thyroid, pancreas, bladder, colorectal, kidney, breast, endometrial meningioma, upper gi, ovarian, multiple myeloma, and prostate and lung cancer. And there was a lower overall cancer risk amongst individuals taking GLP ones compared with those who are not particularly in those that may be associated with hyperinsulinism. So for endometrial cancer for example, that's one that we know is metabolically associated ovarian cancer and meningioma. There was the only one there where there was a slightly increased risk, but it was a not significant increase. Was kidney cancer Again, slight increase, not considered statistically significant, but. A signal worth, paying attention to. Yeah. And further follow up. But again, there wasn't any indication of increased cancer of anything. It was a decreased risk of cancer in patients with GLP ones.

Sonia Singh MD 55:19

So I'm assuming then in this study that they did not separate out or exclude people with obesity related or, other signs of metabolic dysfunction. Like this was just anybody who had a BMI over 30%?

Rebecca Berens MD 55:33

Yes. Yes.

Sonia Singh MD 55:34

Yes. Okay. So your beef with this would be like if you parsed out the people who did not have any metabolic dysfunction, perhaps you would not see this relationship.

Rebecca Berens MD 55:44

I think there's, obviously, there's a co variance where a lot of people who have metabolic dysfunction have they gain weight as a result of that. That's like a si, that's a symptom of their metabolic dysfunction, right? It's they're more likely to be at a higher weight, but I don't believe that being at a higher weight automatically means you have metabolic dysfunction. So it's they co-occur, but they are not causal necessarily.

Sonia Singh MD 56:05

Okay. Okay. The

Rebecca Berens MD 56:08

cause and effect is going a different direction. Is my,

Sonia Singh MD 56:12

Okay. So let's talk a little bit about mental health side effects or how these, we have GLP one receptors actually all through our body. I think a lot of people think it is like working on your gut and it's just in your gut, but really there's GLP one receptors everywhere, as we've learned from rodents who apparently have a lot of GLP one receptors on their thyroids.

Rebecca Berens MD 56:30

Yeah. So in some of the initial pharmaco vi vigilance studies, there was an indication of a possible increased risk of depression, anxiety, and suicidality with semaglutide in particular. But subsequent meta-analysis did not show an increased risk, and they attributed this to an underlying psychiatric risk in this population rather than a direct drug effect. And so this comes back to what I was talking about before, like people who every time they go to the doctor get harassed about their weight and live with the stigma of their weight in society are at an increased risk of psychiatric disorders. And so I think that is something that that, that was shown in these pharmaco visualists as they were picking this up. And since it doesn't appear to be a direct drug effect, because the subsequent meta-analysis ruled that out. It's something to do with the population of people that was taking these medicines that made that pop up in the pharmacovigilance studies. So this is like after the drugs are approved and we're looking at the adverse reactions that are reported and these things are coming up and I think it, it indicates are were these people maybe having these issues and not seeking healthcare previously and now they're going for, to get this drug and now they're having this identified that maybe previously wasn't identified before. Or is there anything to the experience of taking the medication, experiencing weight loss, experiencing the effect of that in your life that affects your mood? I've also had some patients tell me that once they started taking their GLP one, they felt like there was no joy in food. Yeah. Which sounds very depressing.

Sonia Singh MD 58:04

Yeah.

Rebecca Berens MD 58:04

I think it's an important thing to consider that we should be monitoring this very carefully because this is a situation where people who are vulnerable and are at high risk, are maybe not being properly screened and treated, and the focus is on the weight and not on the big picture of what's going on for that person.

Sonia Singh MD 58:27

Yeah. Honestly, I'm surprised that there's not more research or more just general talk around this topic. 'cause I think, especially for women Food and eating and weight just carries so much emotional baggage, and I can't imagine that an intervention like this would not have profound effects on them in either direction, I don't know. I'm just surprised that there isn't more research on this topic. But and I, anecdotally, I've had two patients stop these meds because one told me like, I just don't get pleasure outta food anymore. And it feels like it's taken away this big. Joy in my life. And like another one who was like, I definitely feel like I get depressed when I take this medicine. It works, but I get very depressed and I don't wanna take it anymore. I'm I believe that there's probably, definitely something, there's some interplay of underlying risk factors and what's happening with the medication. But yeah, I'm curious to see what the future holds in terms of research in that area.

Rebecca Berens MD 59:21

Yeah. And another thing that I thought was really interesting from this pharmaco vigilance study, they said the increasing popularity of semaglutide as a treatment for obesity has been fueled by media coverage and social networks resulting in a surge in sales and shortages globally, as well as the proliferation of illegal sales and counterfeit drugs. Unlike traditional prescription anti-obesity drugs, semaglutide use is often driven by, by media influence, which may attract a different patient population with many users accessing the drug through less regulated channels. Consequently, individuals treated with semaglutide, but may be less likely to receive formal diagnoses or follow-up care, potentially leading to underreporting of adverse events such as depression and suicidality. So that's another key piece of it that's important is the initial studies that are done are one, excluding people with major psychiatric conditions, right?

Sonia Singh MD 1:00:07

Yeah.

Rebecca Berens MD 1:00:08

And then the people that are taking them are, again, different than the people that were studied.

Sonia Singh MD 1:00:14

Right.

Rebecca Berens MD 1:00:14

And so it, it is really important not to apply. The results of a study population that doesn't match you to yourself. Yeah. And

Speaker 3 1:00:23

yeah,

Rebecca Berens MD 1:00:23

I, I have also heard from from numerous of my colleagues in the eating disorder treatment world of patients who are obtaining these medications often through like asynchronous telehealth platforms or med spas. And misusing them, having complications related to eating disorders. And eating disorder is another one of the mental health side effects that is reported. And was reported in this pharmacovigilance study. There were significant signals for anxiety, mood disorders and suicidality and eating disorders with all three. And the meta-analyses to remove this effect from, for depression and suicidality did not remove it for eating disorders. It's not commented on.

Sonia Singh MD 1:01:09

Interesting.

Rebecca Berens MD 1:01:10

So if you have a patient who is coming in who has been chronically dieting, been struggling with their weight their whole life, the risk of that person having an eating disorder is fairly high.

Sonia Singh MD 1:01:18

Yeah.

Rebecca Berens MD 1:01:19

I don't think most people are screening for it or asking the right questions.

Sonia Singh MD 1:01:22

Yeah.

Rebecca Berens MD 1:01:22

I don't think a lot of people are. Monitoring it, and especially if the person is getting it on an asynchronous telehealth platform or at a med spa by someone who probably is not fully trained to actually administer and counsel on that medication. There's significant risk there and I think that may, that's a really important thing to be considering.

Sonia Singh MD 1:01:43

Yeah. A lot of the horror stories I've heard about GLP ones are from people who were using them from an asynchronous platform or from a med spa, and almost universally they will tell me that nobody really counseled them on any possible side effects, any risks, like what it might be like to, I had one patient who didn't that, got the prescription and then was using it for a while and then didn't use it for several months, and then picked up like a very high dose and took, it felt awful. I've heard stories of people sharing it with their friends and family and they're those people feeling awful. So yeah, I do think, like we talked about at the beginning of the episode, this rise of direct to consumer marketing in various ways or people getting knowledge and information about these drugs completely bypassing any medical professional that might counsel them or determine if it's appropriate or, really give them true informed consent. They're just able to jump into it there. I think there was a whole article in the New Yorker or something about women DIYing their own weight loss regimens. And I think it's incredibly common and scary.

Rebecca Berens MD 1:02:43

Yeah. Yeah. And then we,

Sonia Singh MD 1:02:45

Let's talk a little bit about, I think you wanted talk a little bit about more about marketing and the cost associated

Rebecca Berens MD 1:02:50

with it. Yeah. So I would consider the cost of risk, right? Yeah. Because if you're gonna get the actual real drug, the FDA approved from the manufacturer drug it's gonna range between 149 to 499 a month depending on the dose and the formulation that you get. And that's if you're using a cash pay discount. If your insurance covers it, maybe it's less than that, but increasingly I have patients who were on it, whose insurance previously covered it and now they don't. Yeah. Or they do quote unquote cover it, but they have to meet a deductible first. So they have to pay $1,200 a month for three months for something before it's actually covered. No, that's favorite. It's and again, because of that, the, because of the weight cycling to me if we can't guarantee that someone can consistently, reliably access this drug in a way that is sustainable for them, that is a real risk for the weight cycling.

Sonia Singh MD 1:03:42

I see what you're saying. Yes, and I think that's a fair consideration. I guess what's popping up in my mind. Is. But what about the sustainability of just diet and exercise and lifestyle change? Because I don't have the data or the statistics on this, but I think what we know is that achieving significant weight reduction with diet and lifestyle is hard and then maintaining it for a long period is even harder. It is an intervention with actually surprisingly low rates of long-term success. So I guess my question would be how do you think the sustainability compares? I don't know if we have the data to answer that, but what do you think?

Rebecca Berens MD 1:04:22

Yeah, no, so you're right there. Is there I will actually see if I can find some sources to put in the, in the end here about about sustainability because yes, intentional weight loss attempts have horrible sustainability. Which is one of the reasons why I think that it's a very bad medical advice to prescribe to someone is just lose weight. I'm like you can't sustainably do that safely. But so yeah, that, that is an issue. And I think this is where we are weighing risks and benefits, right? And so if you are able to sustain some lifestyle changes that maybe don't reduce weight, but do help control your condition, that is beneficial.

Sonia Singh MD 1:05:00

Okay.

Rebecca Berens MD 1:05:00

And if you are not able to sustain lifestyle changes that help control your condition, then yes, I think we should use medication as a tool to help patients. The beef I have is with equating it with weight loss because I do think if we are very aggressive with trying to get weight loss and then that is not sustainable, we are playing into this weight cycling issue. And there are other medications that can be used that are not GLP ones that are cheaper and don't have the same weight reduction, but do still control conditions. Are you talking

Sonia Singh MD 1:05:32

about things like metformin?

Rebecca Berens MD 1:05:33

Yeah, so I do use Metformin a lot and I think Metformin is really for now. A really good option because it's cheap and easy to access and very well tolerated for the most part. And like I think we have to give full informed consent to patients about this is a lifelong issue and these are the options for treating it. And coming on and off of this might actually be worse for you than something that you can sustain long term. So if a GLP one is not sustainable for you long term, maybe metformin is something we should start with. And see how we do with that, right? So I think that's the, that's my main issue is just considering all of the risks and benefits of that. And I don't think that the right call is just, everyone should go on these and then, yeah, okay. Two years down the line, I don't have $500 a month anymore to keep paying for this. Yeah. Or, whatever else has happened and I, for whatever reason, I have to stop it and now we're in a different spot. Yeah. So I just, I think it's part of the conversation that I think is. Is lacking, generally speaking.

Sonia Singh MD 1:06:29

Yeah, I would say a clinical scenario that I've seen a few times is somebody who has been dieting for a long time and they've been gaining and losing, 20 pounds or something, and the same thing happens. They get into a good groove, they're making the lifestyle changes, they're doing it consistently and then they get down to a certain weight and then their perception is oh, I just fell off the wagon. Or I just got, like I got lazy, or I whatever. Which I always correct them and I don't think that's the case at all. I actually think there's extremely powerful metabolic changes that are happening that are driving, their food choices and their movement, and a lot of those things that are not happening on a conscious level. And so all of those changes are then making it harder and harder for them to remain restricted in whatever way they're restricting. And so suddenly they'll start being like, huh, I don't, I started having intrusive thoughts about eating a donut. I don't even like donuts. Or, and again, I think we, as a society, and even as medical doctors, there's this idea that's just willpower and personal choice. And I just, I don't think that is the case at all. I think there is a very complex per, set of metabolic processes that are driving that. But then they'll get down to the weight and then they'll slowly start to regain it, and then they'll be like, oh my God, I've gotten, I've, it's gotten too much. I gotta get this under control. And then they'll go back down. And so for somebody like that, I see that they're, they're on this roller coaster and in my mind I think, okay, we could also try this medicine. And with you having the awareness that this is also a long-term situation, just as I always remind people, any intervention you do for weight loss is a long-term. Intervention, like whether you do diet and exercise, it's not like you can just do it for a certain number of months and then be like, I'm going back to the way I was doing it before, and maintain that. That's very unlikely. Or bariatric surgery. Even people who get part of their stomach removed or part of their stomach in intestine like that, you have to continue eating in accordance with what what fits in that smaller stomach in order to maintain that weight loss. And you can gradually stretch it out with time and, gain back the weight. So literally there is no intervention where you just do it one time and then you're done with it and you can just go back to the way you were before. So always make that point with people about GLP ones. Yeah. But so as long as their understanding of that, that look, this is not a one and done, or this is for a few months and then I'll never have to do it again. As long as you understand that this is a long-term solution, is it going on this and then bringing you down and then just keeping you there better than them going through this cycle of gaining and losing, and then all the guilt and shame and self blame and stuff that happens along that process. That's something that I think about often with people when I'm talking to 'em about these meds.

Rebecca Berens MD 1:09:15

Yeah. So I think my question would be it depends where you're starting from because if you didn't have any metabolic issues to begin with Yeah. What were we treating? If you did have metabolic issues to begin with, then yeah. I think that this is a great way of managing that. But like even still, you still have to do we talked about the bone density. You still have to do the exercise to maintain

Sonia Singh MD 1:09:35

Yes.

Rebecca Berens MD 1:09:35

Your bone density and your muscle mass. You still have to get all of your macronutrients and micronutrients. Yes. We didn't even get into all of the risks of undereating that can happen Yes. When you don't have any hunger cues and Yes. The, significant nutritional deficiencies that you could have happen. You have to fully weigh the risk amendments and I just think that this is a risk that is just not discussed enough. And so I think, it, you have to, from where the person is starting, you have to be looking at the big picture. What is their current metabolic health status? What is, what are the potential risks of us doing this intervention? 'cause your argument of if I am trying to prevent it getting worse in the future, it's like uhhuh, we could also just wait. Does it, is there actually data that shows that it's better to intervene on this early? I would argue that data actually says the opposite. Because when we start intervening early and we cycle, we make it worse. So I would argue it's actually better to wait until there's sign of a problem before we start putting you on stuff. But I think it is also a patient autonomy. Discussion as well. Because if a patient, knows their family history and they're like, I have all this stuff in my family. I don't wanna go through what my family did. I know genetically speaking, this is high likelihood for me, and this is something I struggle with. Yeah, I think that's a different conversation, but again, it's the sustainability that, that really matters. And so I just think it's an important consideration to have. And I think we, we have to be clearer about that because I see so many patients say I don't wanna be on a medicine forever. And I'm like if you don't wanna be on a medicine forever, this is not the one for you because you'll have to be on it. And to your point about the metabolic changes and the biological drivers of of, of this these changes. I think if anything, what these drugs have taught us is how biological our drives are. Our hunger. Yes. Our satiation, our cravings. It is still fascinating to me when I see people say, it's just don't pick up the fork. It's just willpower. I'm like, yes. This literally, you put this in and your brain just tells you something different.

Sonia Singh MD 1:11:40

Yes.

Rebecca Berens MD 1:11:41

That shows you how much this is biological, right? Yes. And we are at the end of the day just animals with lots of chemicals floating around in our brain telling us what to do. We think we have a lot of control over how we behave, and we actually do not. Yeah. And so I just think we should be cautious, is all I'm saying. Yeah. And I think that there is inadequate discussion of the impact this has on people psychologically and on the sustainability of these medications for the long term. And also on why is this the way we're fixing this problem when the problem is the environment that we're all in that is Right. Driving us. 'Cause we would follow different behaviors if our environment was set up differently.

Sonia Singh MD 1:12:22

Yeah, absolutely. Yeah.

Rebecca Berens MD 1:12:23

And and so if we could have an environment that was more walkable and had easier access to food and time to prepare, said food, and we're not sitting at desks all day doing jobs on computers. There's a lot of things that contribute to the metabolic health issues that we see in modern society that could be fixed in a different way. But why are we fixing them this way?

Sonia Singh MD 1:12:47

Yeah what you're saying is really I think a big paradigm shift and it will come across that way to a lot of physicians. 'cause I this was back in, this was like 10 years ago at this point, but 2016 when I first came out of residency, I was thinking about getting obesity medicine certified. And so I did a lot of the CME in preparation for that. Never ended up taking the test and doing it. But I remember one of the big take home points that I was shocked by in a lot of that training was really like, at that time the weight loss drugs that were available weren't honestly not that great. But there was a real big emphasis on use them liberally. Because even if you get some weight off of somebody for a few years, potentially you are giving them some benefit, which is very different from what you were saying. And this was 10 years ago. So perhaps a lot of the data has now shifted in a different direction of no that transient weight loss is not maybe as beneficial or panned out to be as beneficial as you thought. But that was the messaging that I got in my, a lot of my previous education and training, which is okay, even if we do this for a few years and you decide this is not right for you and you don't wanna continue it, perhaps we have gotten benefit out of that. And I guess I don't know that we have really proven that one way or another. I don't know that there's data on that.

Rebecca Berens MD 1:13:58

Yeah, I just think that Both the, the weight cycling data that's out there.

Sonia Singh MD 1:14:02

Yeah.

Rebecca Berens MD 1:14:02

And the observed experience that I have and that you have as well of patients doing this on and off thing, it's psychologically taxing, it is physically taxing, is metabolically taxing. And I think that I am not against the use of this tool. I, I wanna be very clear about that. I think that GLP ones are a wonderful tool for the right patient. I just think we have to be counseling appropriately and we have to be monitoring appropriately. And I think that is the part that is often not happening. Particularly when someone is getting it from a med spa or from a asynchronous telehealth platform and they've never actually had a synchronous conversation with a healthcare provider about it. I think it's just, really important that we're being very clear about what the data does and doesn't show. And if we're gonna choose to use a tool that we use it properly for the intended uses that we have data supporting benefit.

Sonia Singh MD 1:14:56

I totally agree with you. And I think a lot of our conversations on this podcast boil back down to informed consent and whether people are getting informed consent for these decisions that they're making. And, a common theme is just that it's unlikely to happen in social media settings and that honestly, even in doctor's offices, there often is not the time and the bandwidth of many providers to, have this complete of a conversation. We've talked about this for over an hour at this point. Imagine what fraction of that can possibly be communicated in an office visit.

Rebecca Berens MD 1:15:29

Yeah,

Sonia Singh MD 1:15:29

hard. Okay. You we've alluded a little bit to, to compounded formulations of GLP ones, but let's talk a little bit now about what a compounded GLP one is and what additional risks might come with that.

Rebecca Berens MD 1:15:42

Yeah, so I just wanted to bring that up as another risk to consider because of course there are FDA approved. Versions of these drugs available direct from the manufacturer and through retail pharmacies, but they are expensive. And so a lot of people do choose to go a compounded route because it is slight, slightly cheaper and it is often easier to access. And especially when there were significant shortages of these drugs during the high demand peak time you couldn't get the brand name from the pharmacy. They just didn't have it in stock and they hadn't set up their direct to consumer sales yet. So there was just no other way for people to get it. So this is how they were getting it. And so anyway the FDA has put out a statement on compounded GLP one drugs and they said they're aware of fraudulent compounded semaglutide and tirzepatide marketed in the US that contains false information on the product label. In some cases, the compounding pharmacies identified on the labels of the products do not exist. In other cases, the labels of the fraudulent compounded medicine contain the name of a licensed pharmacy that based on the information the FDA has gathered did not compound these products. So some of them are just frankly fraudulent, not even,

Sonia Singh MD 1:16:48

yeah.

Rebecca Berens MD 1:16:49

What they say, they are not made by who they say they are. Compounded drugs in general, pharmacies are taking the ingredient. For the medication and making it themselves because the formulation from the manufacturer is not available. That's usually the time when compounds are produced. And so during the shortages, that's when this really blossomed. But it's also like where are they sourcing it from? Often, not very clear. I had a lot of patients ask me about this, especially during that peak time, and I called several compounding pharmacies that patients asked me about and asked them about their sources of their medication. And I got very unsatisfying answers, as you can imagine. No one wanted to tell me anything, and I was like, why would I prescribed you something that you can't tell me where it came from?

Sonia Singh MD 1:17:31

Yeah.

Rebecca Berens MD 1:17:32

So that, that was a big concern that I had. The other concern with compounds is there is I important storage requirements for these medications. They require refrigeration for the injectables, for example. And so that there, if there are, compounded products that haven't been stored correctly. There's just less regulation of that process. Yeah. There could be impact there on the efficacy and safety of those medications. There's also some salt forms of the peptides being created, which I don't fully understand this, but it's basically not the exact same form. It's a salt form of the peptide. Okay. That is being used in compounds. And this is not the exact same thing. This is a slightly different version, so we actually don't know if it behaves in the same way in the body and if there are different side effects or risks to consider 'cause that has not been studied. So that's really important to be aware of. And then there are potential side effects associated with the compounded versions that may not be submitted because they're not regulated in the same way that traditional pharmacies are. And so there may not be these reports of adverse events being given to the FDA. And then as you alluded to in the peptides episode there have been versions sold that were for research purposes, not for human consumption that have been sold as as drugs as well. So yeah, there's a lot of risks to compounds and again, for me it's also the sustainability of if the pharmacy that was producing it for you all of a sudden gets shut down because it turns out they were doing something shady. Now where do you get it? Yeah. So if you could only afford it when it was compounded and now it's no longer available to you, compounded, then what is the downstream effect of that?

Sonia Singh MD 1:19:13

Yeah, the analogy I always use with my patients about the compounded meds, so I don't prescribe them, I don't think you prescribe them. And by the way, FYI, you and I have no relationships with

Rebecca Berens MD 1:19:22

no,

Sonia Singh MD 1:19:23

Eli Lilly or any other pharmaceutical companies. So we're not financially motivated to make people take the brand name pharmaceutical in any way. But the analogy that I often use is knockoff handbags. So like a compounded mat is like a knockoff handbag. You can have really high quality fakes that look exactly like the real thing and that are made in the factory next door, like made in the same factory. And they can be fine and they can work, but you can also have a fake that looks like the real thing and then falls apart in a week. And with a compounded drug, there's just no way for you as the consumer or even the prescriber to really have any idea if it's a good fake or a bad fake, and so I always remind people you're just you're taking on an additional risk, which at the very least you have to be aware of, in the height of the shortages. I had patients who legitimately really did probably need these drugs or, were benefiting from them hugely and could not afford to get them through, their insurance would stop covering or never covered or, they couldn't they couldn't get it at the pharmacy. So I can understand why people, patients and consumers go to these options. But again, they need to be doing it with full understanding of the additional risk that they're taking on. So we talk a lot more about that in the peptide episode. But yeah, and anytime I think there's a gold rush like this in medicine, where suddenly your gynecologist and a random ER doctor and in random urgent care down the street, everybody's selling compounded GLP ones. I think you really have to step back and be like whoa. How motivated are these people to ensure the quality and safety of this product? Are they calling and looking into the supply chain? I bet you they are not. This is where I think you really have to be a savvy consumer and think critically about. Where you're going for some of these products.

Rebecca Berens MD 1:21:01

Yeah. I love that analogy. The knockoff handbag. I'm gonna use

Sonia Singh MD 1:21:03

that. Yeah. That's the one I use the most. So what can we learn from this as doctors and as humans?

Rebecca Berens MD 1:21:10

I think the biggest thing for me is we have to make sure that we are not extrapolating evidence to people who were not included in studies. And I think there is a lot of extrapolation of cardiovascular benefits to patients that were not in those cardiovascular studies.

Sonia Singh MD 1:21:31

Yeah.

Rebecca Berens MD 1:21:31

And the patients that were in just the weight loss studies, there was much less, but still some medical outcomes that were seen. And so I just think we have to be very clear on what are the true risks that we know of? What are the true benefits that we know of? And for this patient in front of me, how do those weigh out? And I think that's the key thing for me. And it, it does mean that you could have two patients that look very similar who may make very different decisions based on their personal lifestyle risk profile concerns related to disordered eating or mental health or whatever it is. And neither one is wrong, but it has to be fully informed and I think that's what is often missing. And I think as doctors. We should be very thoughtful and cautious about using medications, any medication that influences a person's brain in particular. And just making sure that we're taking in into account all of the considerations and not flippantly prescribing and, blindly following a guideline that may or may not be based in the best evidence for that patient.

Sonia Singh MD 1:22:42

So again, it's interesting because I mentioned this at the very beginning of the episode because I think the population has a certain this applies to them in a certain way. And then in my population, I'm much more likely to have a patient who you know, has sleep apnea or has diabetes and is really reluctant to go on one of these medicines because of the fear around it, or the stigma or this feeling of shame of it being an easy way out or I should just be doing better with my diet and exercise. I've had multiple patients like that who had a clear indication where they may benefit from this, and there was anxiety about potential side effects. Usually those are fairly straightforward to talk through. But the bigger barrier was this idea of but I should just be able to do this on my own. And I would say the message, that I wish I could share with more people and that I try to talk about a lot in my practice is, this idea that it's a moral failure or a personal failure or a failure of willpower or discipline is just not physiologically or medically founded. It's not that simple. To boil it down to that is, is it's just not accurate. It's not true. And so I think really, treating when there is metabolic complications, treating them as such and understanding that there are these, like you said, really powerful physiologic, chemical hormonal drivers that are leading to these outcomes. I just, I would just wanna emphasize to people to not forget that piece and to not treat it as though this is, oh, it's just a shortcut. It's an easy way out. 'cause I really think a lot of people. Don't even consider it or feel like they shouldn't be on it because they believe that, and I think that just keeps them stuck in this cycle of guilt and shame and self blame and maybe help, holds them back from using a tool that could potentially be very useful for them. So it's funny 'cause like I feel like I am constantly dealing with the opposite patient where I'm like, I really think you could, if you wanted to try this, we could do this. But obviously with a, careful selection, discussion of their values and priorities, understanding of the risks that it is long-term. All of those things.

Rebecca Berens MD 1:24:48

Yeah. And I think, I actually have a lot of similar conversations 'cause I have a lot of patients who have a history of an eating disorder Yeah. And is no longer active. Yeah. And now they're older and there are some metabolic health concerns and it's been brought up and they're like, I don't wanna go back into my eating disorder.

Sonia Singh MD 1:25:04

Yeah.

Rebecca Berens MD 1:25:04

And they're fearful for that reason. And I think it's, we have the conversation and some of them choose to proceed and some do not, but at least the conversation is being had. Yeah. And I don't think that it's fair on either side. I don't think it's fair to say you should not use this because it's too dangerous for you and because this happened to you in the past. And so now we're just not gonna treat your metabolic health problem. That's not fair. But it's also not fair to be like to. You might get a metabolic health problem in the future because your BMI is this, so we should just give you this medicine now. I also don't think that is,

Sonia Singh MD 1:25:38

yeah.

Rebecca Berens MD 1:25:38

Is it a thorough or appropriate approach? So I think it's just the thoroughness and I think as you alluded to there's so many people now adding this on because there's demand. It's the gold rush.

Sonia Singh MD 1:25:49

Yeah.

Rebecca Berens MD 1:25:49

And are they doing it thoughtfully? Are you receiving care thoughtfully? I think that is the important piece for a patient to be looking for. I think the other piece too is there probably is gonna be more and more data coming out about these other uses for the medications. Like for substance use, for example. And other uses outside of metabolic health. I've already heard talk of it being used for binge eating, and there's a lot of fear within the eating disorder specialist community about how this is going to play out if we, if it gets approved for binge eating, for example. Because it's so difficult to parse out sometimes, especially if you don't have a lot of experience. And is it binge eating because you were previously very restricted and this is actually normal

Sonia Singh MD 1:26:33

right.

Rebecca Berens MD 1:26:34

Eating to recover after a period of significant restriction. Or is it, on the kind of inappropriate hunger cues related to insulin signaling issues or, other hormonal issues or whatever. So it's it's gonna be really tricky and more of this is gonna come out and so we need to be constantly reviewing what is the actual data that we have now and factor that into informed consent and not extrapolate future possibilities into current practice before we really know. 'cause that's really not informed consent.

Sonia Singh MD 1:27:07

Yeah. I'm going back a little bit here, but we didn't talk about food noise and this whole, all the chat, talk about food noise. So I feel like we should just briefly talk about that. Tell me, give me your thoughts on what you think about the ability of these meds to reduce food noise for people.

Rebecca Berens MD 1:27:25

Yeah. So I think food noise is such an interesting concept because I don't think anyone used the word food noise before 2021. No.

Sonia Singh MD 1:27:32

Yes. It's totally a new phenomenon.

Rebecca Berens MD 1:27:34

And it's how does one differentiate between hunger and food noise? Like we are supposed to have hunger. That is a normal physiological signal. Signal that we're supposed to have.

Sonia Singh MD 1:27:45

Yes.

Rebecca Berens MD 1:27:45

And. We ha we, that is how we survive. Like we get hungry, we eat food, we derive pleasure from eating food that makes us seek out that food. It, that this is how we're wired, right?

Sonia Singh MD 1:27:55

Yeah.

Rebecca Berens MD 1:27:55

And I think what can happen for patients with eating disorders, for example, food noise is, can be a description of what a person with an eating disorder experiences, which is preoccupation around food, like planning food. Yes. Thinking about food, like what am I gonna be eat able to eat something there? I can't eat this thing. What if the, what if this thing has this ingredient, just a lot of, again, noise in the head about food that is a preoccupation about food. And then there is food noise that I think for some people is they are getting hunger signals inappropriately related to disorders of insulin signaling and metabolic issues. If you are if you have chronically high insulin and are chronic chronically insulin res resistant, you are not going to be efficiently using your fuel in a way that signals your brain to have satiety and that is going to make you feel hungry even if you have eaten a sufficient amount uhhuh. And so it's really difficult to distinguish between those two things because a lot of the people that have that food noise also have had disordered eating because they've tried to lose weight before.

Sonia Singh MD 1:29:00

Right.

Rebecca Berens MD 1:29:00

And so you have to be able to tease it out. And before these meds ever existed, this was something that was. Talked about all the time with eating disorder specialists, with these patients of trying to reset and better understand hunger cues. When is it true hunger? When is it emotional hunger? When is it eating for pleasure, just 'cause it's fun? When is it maybe an issue like this is maybe something more medically going on. That is part of what is teased out in eating disorder treatment. And generally the approach is to try to move towards a concept called intuitive eating where you're able to be more in tune with your real hunger cues and eat accordingly to that. And that I get, I think, has been totally broken down from young ages for us because there is such a preoccupation again about weight. And I think a lot of this could be avoided if we did not have that preoccupation from such a young age. I think a lot of the people, like I said that now are in their thirties and forties and dealing with metabolic associated fatty liver disease are people who have done the weight loss cycling over and over again since their teens. And it's built up over time. So I think turning off food noise is not universally a good thing. And we should really understand what food noise means to that patient. And are they going to be able to eat enough Without it, because I think especially I think the general practice initially was just like, titrate up to the highest dose that they can tolerate and they'll get the most weight loss. I'm like, yeah, you could titrate all the up and then maybe they're not eating at all and now they're having significant nutritional deficiencies and

Speaker 3 1:30:32

yeah.

Rebecca Berens MD 1:30:32

Not getting enough protein even and so you have to be very careful about that. And so I don't think turning off food noise is a good thing, but I think it is helpful when patients have inappropriate, cravings and hunger cues when they have been fed adequately and they're getting these hormonal cues that are inappropriate related to their metabolic dysfunction. It is helpful to them to have support with that.

Sonia Singh MD 1:30:54

Yeah, I, you're making such a good point about how heterogeneous, the idea of food noise can be. I think it's easy for us to think of it as one thing, I, in my mind when I think about food noise, I think about a patient who's telling me oh yeah, like it's time to eat breakfast and I gotta make it some, I gotta make something fast. And I'm just like, oh, should I eat this? Or is it better to that or should I eat this? And then I'm thinking about it for too long and then it's draining a lot of energy and then I'm just like, oh, forget it. I'm just gonna have a granola bar. But that is very different than somebody who's having appropriate, hunger cues in response to restriction. It's very different than somebody who like you said, has a pre true preoccupation with food related to eating disorder. So yeah that, that's a great point. That food noise in itself is not necessarily something that needs. Pathology that needs treatment and it's can mean a lot of different things and be a lot of different things. The other claim that I wanted to go back to for a moment, especially in the context of social media, is one of your claims was about GLP one's worsening fat phobia or, further stigmatizing certain body types. I feel this very big shift of, for a long time, or at least in the nineties when you and I were coming of age, the body ideal was this very thin, emaciated heroin chic. I think they called it some point, right? Yeah. And over the next few decades, the ideal body type really shifted a little bit towards a fuller curvier body in a way. I think in some ways that first ideal will always be an ideal, but, I really think there was a shift happening culturally and now it feels like we're gonna go all the way back to, a very extreme sort of malnourished appearance as being maybe the most prominent ideal in terms of media and what we see on social media because of the availability of these drugs and people's ability to easily get to that body type without, heroin, some of the things that they were using before. I don't know. I'm curious about your thoughts about that. That feels to me like a big societal risk and harm that is Happening right now.

Rebecca Berens MD 1:32:52

Yeah, no, it definitely is. And I think I said at the beginning, I've seen people saying things like, now there's no excuse to be fat. It is very stigmatizing.

Sonia Singh MD 1:33:01

Yeah.

Rebecca Berens MD 1:33:01

Because if someone has chosen based on the available risks and benefits not to take this medication

Sonia Singh MD 1:33:08

Yeah.

Rebecca Berens MD 1:33:09

And they have a larger body size now, everyone's what's wrong with you? Which they were already saying that before. But now it's it's like amplifying that, that negativity. And I just think that that is something that, that, that's the reason I feel so, so passionate about, really selecting the appropriate patients who actually really medically are benefiting from this. And not just to meet some sort of societal ideal. Because it's very important that we not send that messaging. And also, I also just wo wonder about the epigenetic changes To our future generations if we have this whole generation that's been appetite suppressed with these medications. 'Cause I, the other thing that I really believe is that, dieting is not new. Dieting didn't start in the nineties. Yeah. Dining's been going on since many years ago. I, you've probably seen the ads from the fifties, like the white wine and boiled egg diet. Have you seen that meme on social media? So it's this been going on, and I do think that has also contributed via e epigenetic changes to some of the metabolic dysfunction that we are seeing today. There, and for anyone listening who's maybe not familiar with epigenetics, so this is the concept that the environment of the mother or, and father results in changes to their DNA methylation that is then transmitted to the offspring and affects the expression of their genes. Yeah. And so it makes sense that someone who has a really restrictive intake as as a, an adolescent or adult and then becomes pregnant and then has a child, there were changes to their DNA that are transmitted to that child that makes that child then more likely to likely avoid starvation. Yeah. And so it, I do think that's another consideration that we have to be thinking about. And I again, don't think that, that's hard to study and it's hard to know, but I think it's real and important to be looking at all of that big picture.

Sonia Singh MD 1:35:05

Okay. So why don't we finish the episode with how we would talk to our patients about GLP ones.

Rebecca Berens MD 1:35:11

So I think the first thing is, as we've been saying, full informed consent risks and benefits in their specific clinical context for what they have going on in their, whether they have pre-diabetes or metabolic associated fatty liver disease or high blood pressure or whatever it is. What is the data actually show and what are the risks and benefits? And then I think for, wait for everyone really we should be screening for disordered eating. I really think we should, because I think it's so much more common than people realize. And I don't know of any PCP that screens for it. Did you ever get any training on screening?

Sonia Singh MD 1:35:45

Never. Never?

Rebecca Berens MD 1:35:46

Yeah.

Sonia Singh MD 1:35:46

And what is an appropriate screening tool or like

Rebecca Berens MD 1:35:49

a so there are a few one is called the Scoff. And the scoff is like a quick five question screening tool. That can be, it could be done in really quickly in a visit. Just five questions. The other one's called the ESP, which is the eating disorder screen for primary care. And I'll link to those in in our substack. But these are quick just a few questions, screeners that, that could be used. And again, anytime you're screening, what are you gonna do with that screening if it's positive, right? You always have to have a plan for your intervention after you've screened. And so you wanna make sure you have the appropriate resources to refer that patient to a dietician, therapist, mental health practitioner someone who is informed about eating disorders. But but I think that is important and I think it's something that it's, if you can have the upfront conversation about it, you can mitigate a lot of harm.

Sonia Singh MD 1:36:39

Yeah. Yeah. I'm also curious to know like how often in PCP visits, it would be really interesting to see like a study on this. Like how often in PCP visits are people having discussions about the nutritional guidelines around what you should do when you're on a GLP one, or the risks around bone density loss and muscle mass loss, and how you can, mitigate those effects. There's a whole, you, I think you put it in the references. There's a whole guideline around, nutritional guidance for patients on GLP ones, but I'm curious how often that really gets discussed, mainly because there's so little time in most PCP visits. So yeah, I think all of that is probably, falls under the umbrella of full informed consent and adequate counseling around these meds.

Rebecca Berens MD 1:37:19

And I really feel, we've talked about dieticians many times. I love dieticians and this is exactly where a dietician should be used because we don't have time in PCP visits or really the in depth education most of the time either to really get into the weeds with the patient Yeah. About about that. And I, I. Strongly recommend that all of my patients that are taking a GLP one are seeing a dietician. Because especially initially just to like really understand, there's so much that changes in how they feel and even just to adjusting to the side effects sometimes it's helpful to have a dietician involved and it can make a really big difference. So I, I strongly encourage that and I always refer patients to see a dietician if they're starting,

Sonia Singh MD 1:37:59

I hear all the PCPs in their cars being like, yeah, but new, the insurance won't cover the dietician unless they have certain diagnoses or I remember that struggle Yeah. Of having a hard time finding somebody to see my patients or like that they were getting it covered.

Rebecca Berens MD 1:38:15

So I have not really had a hard time, I gotta be honest. I, I think maybe it's just, I know lots of Davi savvy dieticians but even now there's also like websites where you can there's several websites where you can go on and find a dietician and granted it's I don't know who some of these people are, but they're all registered dieticians. They have licenses. Yeah. Where you can go and select for like specific conditions that you have. We can maybe link some of these in the substack. But, if you're starting someone on a GLP one, theoretically there is a metabolic issue that you're concerned about.

Sonia Singh MD 1:38:47

Yeah.

Rebecca Berens MD 1:38:48

Right.

Sonia Singh MD 1:38:48

Yeah,

Rebecca Berens MD 1:38:48

that's

Sonia Singh MD 1:38:49

true. Yeah.

Rebecca Berens MD 1:38:49

Theoretically they have high blood pressure or pre-diabetes or hyperlipidemia or there should be a diagnosis. Otherwise, I would also ask yourself if there's not a diagnosis to support seeing a dietician, why am I starting this patient on a GLP one?

Sonia Singh MD 1:39:00

Because a lot of people, I know this is not your practice, but a lot of doctors are going to prescribe it for patients who just have obesity. So like those patients, oftentimes it is not easy to get, I don't know. I haven't been in insurance-based care now for five years. Yeah. So maybe it has gotten easier. I

Rebecca Berens MD 1:39:15

mean I think either they have a metabolic condition that you can diagnose or they don't. And if they don't, I would ask, I would just ask yourself the question, what is the benefit here for this patient? And and also you can also pay cash to see a dietician. And I think that's the other thing that I think a lot of our insurance-based colleagues forget about. And granted a lot of patients do not wanna pay cash to see a dietician, but if you have someone that is really proactive and really wanting to make a difference in their health and they're like wanting to start this medication and they are taking it seriously, they probably want good care. Yeah. And they will probably pay for it. Yeah. And rather than them going and finding their own like random person on the internet with, may not have appropriate credentials, you should at least provide them with some resources if they choose to take it or not. It's up to them, but I think it's good to recommend it.

Sonia Singh MD 1:40:08

Yeah, totally agree. And I've used there's one we're probably thinking of the same one. There's one like big online telehealth platform that has our actual rds and they do take a lot of insurances. And so I've, I have had success with that one. We'll link we're not affiliated with them in any way, but We'll, we will link them in the substack. Yeah.

Rebecca Berens MD 1:40:27

Yeah. And we do have great options locally too. Like we really do. Yeah. We're lucky here in Houston, but I'm sure there are lots of people around the, there's just not a lot of discussion between dieticians and physicians. I've realized. I think because the systems don't prioritize them very much. Yeah. And so they're siloed away. But there's a lot of dieticians out there in private practice who can help your patients.

Sonia Singh MD 1:40:50

Yeah, I think in situations, I've only seen this happen in a few places, but where they're embedded inside of a prim primary care clinic, you're like, oh my God, I can send every patient to you because there's so many, they can be valuable for so many different situations. But I think just the logistics of it make it sometimes challenging for people, but okay. And then so we talked about honesty, about the risks and benefits. We talked about careful monitoring for side effects and perhaps using the minimum dose necessary. And then lastly talking about careful monitoring when people do go on these meds, I really think a lot of times in the situations where it's not being prescribed or it's a compounded product people are just being told, yeah it's fine. You're gonna be fine. There's no side don't worry about anything. No monitoring required. And we talk about this a lot in the peptides episode, but these peptide drugs are drugs and even if you, the ease with which you acquire it is not proportional to the side effects or the safety profile. You still, need a well-trained medical professional prescribing and monitoring these ideally.

Rebecca Berens MD 1:41:54

Yeah. And I think that monitoring part is so key. And, I think, again the, for the minimum dose necessary, like we, there's no rush to this. I also see people like really rushing to taper them up to the highest dose. And I'm just like for why? For why. Because it, to me, that just makes it less sustainable. And we can reduce GI side effects. If we go slow more slowly, we can help the patient adjust and not become nutritionally deficient because their hunger is so suppressed and they feel so nauseous. And then we, maybe they don't have to be on as high of a dose and, eventually, hopefully these companies make these medicines less expensive. Yeah. And people and they don't restrict people from adjusting their doses. 'Cause now that's a big issue. If people could theoretically buy a vial that is a larger dose and then split it up into smaller doses. Yeah. And it would be more cost effective. But of course they don't want them to do that. So that is not currently how they are prepared or sold, but there could be other ways of administering this drug to people in a way that would be more sustainable. And I hope that in the future we'll move towards that.

Sonia Singh MD 1:42:59

Yeah. Okay. Where can people go for more info?

Rebecca Berens MD 1:43:04

So I'm gonna link all of the articles that we talked about today in our substack. And there in particular, there's a great informed consent resource from the medical students for size inclusivity. It is from 2023, so it's a little bit out of date now. Some of the newer data is not included in there, but I think it at least scratches the surface of a lot of the concerns that we talked about. And I think it's a good starting point for people.

Sonia Singh MD 1:43:27

Oh, this is so cool. Yeah, it's like a 10 page PDF with a lot of good information. So that's an awesome resource. Thank you for sharing that. Okay. All right, that brings us to the end of the episode. Thanks Rebecca.

Rebecca Berens MD 1:43:39

Thanks Sonia.

Sonia Singh MD 1:43:44

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