Latest / The Antisocial Doctors Podcast / Episode 13: Are GLP-1s a Miracle, a Mistake, or Something More Complicated?

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Episode 13: Are GLP-1s a Miracle, a Mistake, or Something More Complicated? · The Antisocial Doctors Podcast

• 1:27
  Sonia Singh MD: 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,
• 1:38
  Rebecca Berens MD: and me, Rebecca Barons, a board certified family medicine physician with a special interest in disordered eating.
• 1:43
  Sonia Singh MD: We're also a millennial women anxious moms and curious humans navigating social media.
• 1:48
  Sonia Singh MD: We've seen firsthand how these platforms can be powerful tools for education and connection, but can also make us unwell.
• 1:56
  Rebecca Berens MD: This podcast is meant to be the antidote to your doom.
• 1:58
  Rebecca Berens MD: Scrolling, a, solve for the anxiety, stress, guilt, shame, and confusion.
• 2:02
  Rebecca Berens MD: That comes from social media's messaging around health.
• 2:05
  Rebecca Berens MD: In each episode, we discuss a health related topic, trending on social media with curiosity, nuance evidence, humility, and compassion.
• 2:12
  Sonia Singh MD: This is not your average debunking podcast.
• 2:15
  Sonia Singh MD: We wanna explore not just what is trending on social media, but why?
• 2:18
  Sonia Singh MD: Why are so many people drawn to this?
• 2:20
  Sonia Singh MD: What is the nugget of truth here?
• 2:21
  Sonia Singh MD: What are the facts?
• 2:23
  Sonia Singh MD: What can we learn from this as patients and doctors?
• 2:25
  Sonia Singh MD: No shame.
• 2:26
  Sonia Singh MD: No blame, no snark.
• 2:27
  Rebecca Berens MD: We're so glad you're here.
• 2:46
  Sonia Singh MD: Hey, Rebecca.
• 2:47
  Rebecca Berens MD: Hey, Sonya.
• 2:49
  Sonia Singh MD: Do you wanna start by sharing the patient story that inspired us to talk about this week's topic?
• 2:54
  Rebecca Berens MD: 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.
• 3:04
  Rebecca Berens MD: And it's a lot of people.
• 3:05
  Rebecca Berens MD: It's not one person.
• 3:06
  Rebecca Berens MD: So I just wanna start right?
• 3:07
  Rebecca Berens MD: 'cause I see this all the time.
• 3:09
  Rebecca Berens MD: Okay.
• 3:10
  Rebecca Berens MD: This is a patient with a history of PCOS polycystic ovarian syndrome, pre-diabetes, hyper hyperlipidemia, or high cholesterol.
• 3:17
  Rebecca Berens MD: They've had irregular periods, they've struggled with weight their whole life.
• 3:20
  Rebecca Berens MD: 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.
• 3:28
  Rebecca Berens MD: And as a, as as a result of that, saw multiple doctors Every time they just say, you need to lose weight.
• 3:34
  Rebecca Berens MD: 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.
• 3:43
  Rebecca Berens MD: And they were afraid to start it because of all the scary things that they've seen about it on social media.
• 3:49
  Rebecca Berens MD: 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.
• 3:56
  Rebecca Berens MD: 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.
• 4:04
  Rebecca Berens MD: Yeah this situation,
• 4:06
  Sonia Singh MD: 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.
• 4:14
  Sonia Singh MD: 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.
• 4:22
  Sonia Singh MD: So I really feel like there's this very broad spectrum of conversations that can be had around GLP ones.
• 4:27
  Sonia Singh MD: 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.
• 4:36
  Sonia Singh MD: 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.
• 4:41
  Sonia Singh MD: So it's just, there's a whole there's a whole buffet of conversations that can be had around GLP one.
• 4:46
  Sonia Singh MD: So I'm really excited to cover this topic and kind of, get into the nuances in a little bit more detail.
• 4:50
  Sonia Singh MD: What do you, what would you say, I know there's probably a lot of them.
• 4:53
  Sonia Singh MD: What would you say is the claim around GLP ones that we're talking about today?
• 4:56
  Rebecca Berens MD: 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.
• 5:04
  Rebecca Berens MD: 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.
• 5:16
  Rebecca Berens MD: 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.
• 5:23
  Rebecca Berens MD: And it's amazing.
• 5:24
  Rebecca Berens MD: That's the claim that you hear all the time about these drugs.
• 5:27
  Rebecca Berens MD: 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.
• 5:33
  Rebecca Berens MD: There's those are the two extremes that I always see.
• 5:35
  Rebecca Berens MD: Right.
• 5:35
  Rebecca Berens MD: 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.
• 5:42
  Rebecca Berens MD: You just need to be, do what you should be doing.
• 5:45
  Rebecca Berens MD: And now you're gonna be dependent on this drug.
• 5:47
  Rebecca Berens MD: Just lots of stigmatizing and negative conversations around people who are using GLP ones.
• 5:53
  Rebecca Berens MD: And then in the eating disorder world, actually, it's really interesting.
• 5:56
  Rebecca Berens MD: A lot of the professionals that I'm connected with are therapists and dieticians and other physicians who treat patients with eating disorders.
• 6:02
  Rebecca Berens MD: 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.
• 6:12
  Rebecca Berens MD: And also the impact that it might have on fat phobia and weight stigma.
• 6:16
  Rebecca Berens MD: And so I think there was a very negative push against.
• 6:20
  Rebecca Berens MD: GLP one drugs from that side of the community on social media in particular particularly when the drugs first came out.
• 6:26
  Rebecca Berens MD: 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.
• 6:33
  Rebecca Berens MD: So that's another claim that we will get deep into in this episode.
• 6:37
  Rebecca Berens MD: 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.
• 6:43
  Rebecca Berens MD: And it's all a big conspiracy.
• 6:45
  Rebecca Berens MD: So that's the other big claim.
• 6:46
  Rebecca Berens MD: So that's the list of things that I've seen.
• 6:49
  Rebecca Berens MD: Anything else that you've seen, Sonya, when you've, that's come up for you on your feed or your ads?
• 6:55
  Sonia Singh MD: No, I think you pretty much covered it all.
• 6:57
  Sonia Singh MD: 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.
• 7:08
  Sonia Singh MD: And why would you put a drug in your body and, pay big pharma when you could do this thing naturally.
• 7:15
  Sonia Singh MD: That is the thing I hear, I would say the most often.
• 7:18
  Sonia Singh MD: And so yeah I'm excited to share my thoughts on that.
• 7:21
  Sonia Singh MD: '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.
• 7:31
  Sonia Singh MD: '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?
• 7:44
  Sonia Singh MD: Is the rd gonna be like this doctor?
• 7:46
  Sonia Singh MD: She is giving this person this drug.
• 7:47
  Sonia Singh MD: 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.
• 7:54
  Sonia Singh MD: Yeah.
• 7:54
  Sonia Singh MD: I'm excited to get into it, but
• 7:56
  Rebecca Berens MD: yeah.
• 7:56
  Sonia Singh MD: Tell, tell us why you think this has become so viral.
• 8:01
  Rebecca Berens MD: So like I said, when Wegovy was approved, I think it was in 2021, so you know, this was I.
• 8:08
  Rebecca Berens MD: Peak COVID.
• 8:08
  Rebecca Berens MD: Yeah.
• 8:09
  Rebecca Berens MD: We were all online all the time.
• 8:12
  Rebecca Berens MD: And everyone was concerned about their health in a heightened way.
• 8:16
  Rebecca Berens MD: 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.
• 8:26
  Rebecca Berens MD: And I think, I don't want that to get lost in the weeds here.
• 8:29
  Rebecca Berens MD: GLP one medications have been around, first of all, for a long time prior to 2021.
• 8:33
  Rebecca Berens MD: Yeah.
• 8:34
  Rebecca Berens MD: 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.
• 8:45
  Rebecca Berens MD: Yeah.
• 8:46
  Rebecca Berens MD: Made such a huge difference for patients with diabetes in particular.
• 8:49
  Rebecca Berens MD: And so I think there was legitimate newsworthiness and press around it.
• 8:53
  Rebecca Berens MD: 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.
• 9:05
  Rebecca Berens MD: And, then shortly after Wegovy came Ze and Manjaro and there was a lot of, back to back.
• 9:11
  Rebecca Berens MD: New stuff coming out, people seeing visual representations of the effects that these drugs can have.
• 9:18
  Rebecca Berens MD: And that got shared widely.
• 9:20
  Rebecca Berens MD: 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.
• 9:32
  Rebecca Berens MD: Social media, influencer marketing was already happening prior to that.
• 9:35
  Rebecca Berens MD: But I think it really grew during that time out of necessity.
• 9:38
  Rebecca Berens MD: 'cause that was the way to reach people.
• 9:40
  Rebecca Berens MD: And in the US we've always had direct to consumer drug marketing.
• 9:46
  Rebecca Berens MD: We can have a whole other conversation about whether that's appropriate, but that's always been happening.
• 9:50
  Rebecca Berens MD: But now we have the added place of direct to consumer drug marketing on social media.
• 9:57
  Rebecca Berens MD: Using images of actual people who are actually using these medications and then being paid to promote them.
• 10:03
  Rebecca Berens MD: So just a lot of colliding things all at the same time that made this just really a big topic of conversation for everyone.
• 10:13
  Sonia Singh MD: 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.
• 10:26
  Sonia Singh MD: 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.
• 10:38
  Sonia Singh MD: That was a big shift.
• 10:40
  Sonia Singh MD: 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.
• 10:58
  Sonia Singh MD: They're saying a testimonial, but they're also, making claims about the drug that is a very new phenomenon.
• 11:04
  Sonia Singh MD: 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.
• 11:11
  Sonia Singh MD: Yeah, that shift I think you just cannot under underestimate.
• 11:14
  Sonia Singh MD: 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.
• 11:23
  Sonia Singh MD: I worked with an endocrinologist.
• 11:24
  Sonia Singh MD: She was using it for diabetes.
• 11:25
  Sonia Singh MD: I remember her being like, this drug it's amazing.
• 11:27
  Sonia Singh MD: This is a phenomenal, like you said, it's revolutionary.
• 11:29
  Sonia Singh MD: Yeah.
• 11:30
  Sonia Singh MD: This is a shift.
• 11:30
  Sonia Singh MD: And she was just like this thing works so well.
• 11:32
  Sonia Singh MD: This is gonna replace Metformin.
• 11:34
  Sonia Singh MD: And I remember being like, oh wow, okay.
• 11:36
  Sonia Singh MD: Yeah.
• 11:36
  Sonia Singh MD: We're using it, my diabetic patients.
• 11:39
  Sonia Singh MD: 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.
• 11:51
  Sonia Singh MD: And I feel like that was when just the pop culture zeitgeist just started to be like, whoa, what is this thing?
• 11:57
  Sonia Singh MD: 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.
• 12:06
  Sonia Singh MD: And within a matter of months it felt like it was then flooding, compounded pharmacies and patients were coming asking for it.
• 12:13
  Sonia Singh MD: And people were finding ways to pay cash.
• 12:15
  Sonia Singh MD: 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.
• 12:23
  Sonia Singh MD: They were drinking more, they were eating more.
• 12:25
  Sonia Singh MD: Not everybody, some people got more fit during the pandemic, but.
• 12:28
  Sonia Singh MD: I do think there was this really big, perfect storm of all of these factors happening at the same time.
• 12:35
  Sonia Singh MD: 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.
• 12:47
  Sonia Singh MD: 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.
• 12:54
  Sonia Singh MD: 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?
• 13:03
  Sonia Singh MD: Can you get, do you have a way to get it?
• 13:04
  Sonia Singh MD: Do you know which pharmacies have it in stock?
• 13:06
  Sonia Singh MD: Do you know how I can get my insurance to come?
• 13:07
  Sonia Singh MD: 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.
• 13:30
  Sonia Singh MD: It is a big deal legitimately.
• 13:32
  Rebecca Berens MD: Yeah.
• 13:32
  Rebecca Berens MD: Yeah.
• 13:33
  Sonia Singh MD: Okay.
• 13:33
  Sonia Singh MD: 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?
• 13:39
  Rebecca Berens MD: Okay, so I think as with any medication.
• 13:42
  Rebecca Berens MD: There are benefits and there are risks, and this is a medication, which in particular the benefits can be very great.
• 13:49
  Sonia Singh MD: Yeah.
• 13:49
  Rebecca Berens MD: And in some patients, the risks can also be very great.
• 13:52
  Rebecca Berens MD: And so it is a situation that requires nuance and careful prescribing and monitoring.
• 14:00
  Rebecca Berens MD: And I think it is true that they have very beneficial for some people.
• 14:03
  Rebecca Berens MD: It's also true, they're very risky for other people.
• 14:05
  Rebecca Berens MD: So we need to just be mindful of that.
• 14:08
  Rebecca Berens MD: But it doesn't need to be all or nothing.
• 14:11
  Rebecca Berens MD: It's not like it's the best thing ever or it's the worst thing ever.
• 14:13
  Rebecca Berens MD: It's depends on the patient, depends on the situation and requires nuance.
• 14:18
  Rebecca Berens MD: And we'll get into all of that with when we get into the facts.
• 14:21
  Rebecca Berens MD: And then I think the other thing is weight stigma and bias in healthcare and in life in general is a huge problem.
• 14:28
  Rebecca Berens MD: 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.
• 14:38
  Rebecca Berens MD: I've seen things, just horrible things like that, that are coming out of it.
• 14:42
  Rebecca Berens MD: 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.
• 14:50
  Rebecca Berens MD: But also they are providing a treatment option for some metabolic health conditions that we didn't really have good treatment options for before.
• 14:58
  Rebecca Berens MD: 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.
• 15:07
  Rebecca Berens MD: But it's a both and situation as with so many things.
• 15:10
  Rebecca Berens MD: And so we have to be mindful and have a nuanced discussion at an individual level.
• 15:16
  Sonia Singh MD: Yeah.
• 15:17
  Sonia Singh MD: Okay.
• 15:17
  Sonia Singh MD: Let's get into it then.
• 15:18
  Sonia Singh MD: Maybe we can start with just laying the groundwork of what is a GLP one drug and how does it work?
• 15:24
  Sonia Singh MD: What does it do in your body?
• 15:25
  Sonia Singh MD: Can you go over that for us?
• 15:27
  Rebecca Berens MD: Yeah.
• 15:27
  Rebecca Berens MD: So the GLP one stands for glucagon-like peptide one, and these are GLP one receptor agonists.
• 15:33
  Rebecca Berens MD: It means they act like glucagon-like peptide one in the body.
• 15:36
  Rebecca Berens MD: Okay.
• 15:37
  Rebecca Berens MD: And as I said, these have been around for a long time.
• 15:39
  Rebecca Berens MD: The first was approved in 2005 for diabetes, which was byta or Exenatide, and there's been several others approved since then.
• 15:45
  Rebecca Berens MD: The first that was approved for weight loss, not for diabetes was Saxenda, which was approved in 2014.
• 15:51
  Rebecca Berens MD: So it's not even new to have these medications be approved for patients without diabetes.
• 15:56
  Rebecca Berens MD: Which I think is a misconception.
• 15:58
  Rebecca Berens MD: I think a lot of people think that Wegovy was the first time that was the case, but that was not the case.
• 16:02
  Rebecca Berens MD: 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.
• 16:16
  Rebecca Berens MD: 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.
• 16:27
  Rebecca Berens MD: 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.
• 16:39
  Rebecca Berens MD: And then an oral form of wegovy was actually approved in December of 2025.
• 16:43
  Rebecca Berens MD: So there's also now an oral form of wa govi.
• 16:45
  Rebecca Berens MD: And so Wegovy, Ozempic and rybelsus all are the same ingredient.
• 16:49
  Rebecca Berens MD: They're all semaglutide or semaglutide.
• 16:52
  Rebecca Berens MD: I don't know actually how, which way you're supposed to say.
• 16:53
  Rebecca Berens MD: I've heard it both ways.
• 16:54
  Rebecca Berens MD: But I think there's also a lot of confusion about what does that mean?
• 16:58
  Rebecca Berens MD: So Semaglutide or semaglutide is the generic name for the medication that is included in Wegovy, rybelsus, and emic.
• 17:04
  Rebecca Berens MD: They're all the same medication, just branded differently, and approved for different indications.
• 17:10
  Rebecca Berens MD: 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.
• 17:19
  Rebecca Berens MD: So it's a GLP one, same as Wegovy Ozempic, but also has some effect on glucose dependent insulinotropic peptide receptors as well.
• 17:29
  Rebecca Berens MD: And so it has basically dual action.
• 17:32
  Rebecca Berens MD: So that was approved in 2022 for diabetes as manjaro and in 2023 as Zep bound for weight loss.
• 17:38
  Rebecca Berens MD: And so both of these medications act similarly.
• 17:42
  Rebecca Berens MD: Again, just the the Manjaro and Zep, which the generic name is Tirzepatide are, have the dual action.
• 17:48
  Rebecca Berens MD: But the similar downstream effects are they slow gastric emptying.
• 17:51
  Rebecca Berens MD: So meaning it slows down the movement of food out of the stomach.
• 17:54
  Rebecca Berens MD: It reduces glucose levels by increasing insulin secretion and decreasing glucagon.
• 18:00
  Rebecca Berens MD: 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.
• 18:08
  Rebecca Berens MD: 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.
• 18:15
  Rebecca Berens MD: 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.
• 18:25
  Rebecca Berens MD: And so that's one of the ways that this drug is helping and why it was being sought out for diabetes.
• 18:30
  Rebecca Berens MD: 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.
• 18:42
  Rebecca Berens MD: And so it can suppress appetite and it also reduces what they call hedonic eating, which I hate that term.
• 18:48
  Rebecca Berens MD: But basically the pleasure of eating for pleasure.
• 18:50
  Rebecca Berens MD: It reduces the pleasure feeling that you have with eating.
• 18:53
  Rebecca Berens MD: 'cause we are supposed to feel pleasure when we eat because that is how we are driven to eat as humans.
• 18:58
  Rebecca Berens MD: 'cause it's required for survival.
• 19:00
  Rebecca Berens MD: And so it does decrease that.
• 19:01
  Rebecca Berens MD: And so hopefully that was a reasonable summary of basically how these drugs are work and what they are.
• 19:07
  Sonia Singh MD: Yeah, that's a great overview.
• 19:08
  Sonia Singh MD: And we have an entire episode on peptide based drugs and peptide therapeutics.
• 19:13
  Sonia Singh MD: And anything that ends with a tide is usually a peptide.
• 19:15
  Sonia Singh MD: So both tirzepatide and semaglutide are actually peptides.
• 19:19
  Sonia Singh MD: So keep that in mind as you navigate the world of peptides on social media as well.
• 19:24
  Sonia Singh MD: Okay.
• 19:25
  Sonia Singh MD: So can you go through what the data shows on the benefits of GLP ones and why they're so revolutionary?
• 19:33
  Rebecca Berens MD: Yeah.
• 19:33
  Rebecca Berens MD: I focused mainly here on the data in patients.
• 19:37
  Rebecca Berens MD: 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.
• 19:44
  Rebecca Berens MD: They they work very well to control blood sugars and diabetes.
• 19:48
  Rebecca Berens MD: 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.
• 19:59
  Rebecca Berens MD: So I don't think that's controversial.
• 20:01
  Rebecca Berens MD: So I didn't dig deep into that data because I didn't think that was part of the
• 20:05
  Sonia Singh MD: I think that's
• 20:06
  Rebecca Berens MD: fair.
• 20:06
  Rebecca Berens MD: There's a lot to talk about.
• 20:07
  Rebecca Berens MD: So anyway, so just to be clear, this is mostly gonna be focusing on the benefits outside of control of diabetes.
• 20:13
  Rebecca Berens MD: So the first one I wanna talk about that I think is commonly discussed is the cardiovascular benefits.
• 20:19
  Rebecca Berens MD: 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.
• 20:35
  Rebecca Berens MD: And by that patients who already have diabetes or already have cardiovascular disease.
• 20:39
  Rebecca Berens MD: So this is not in just the average person out in the world, these are people who are high risk patients.
• 20:45
  Rebecca Berens MD: And this is coming from a systematic review and meta-analysis of almost a hundred thousand patients.
• 20:49
  Sonia Singh MD: So it also sounds like it does not include.
• 20:52
  Sonia Singh MD: Just hyperlipidemia, like just high cholesterol.
• 20:54
  Sonia Singh MD: Is that fair?
• 20:55
  Sonia Singh MD: Correct.
• 20:55
  Sonia Singh MD: Because that is very common.
• 20:57
  Sonia Singh MD: 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.
• 21:04
  Sonia Singh MD: Should I try this?
• 21:05
  Rebecca Berens MD: Yeah.
• 21:06
  Rebecca Berens MD: 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.
• 21:13
  Rebecca Berens MD: You cannot extrapolate the results for one study population to another person who would not have fit in that study population.
• 21:20
  Rebecca Berens MD: So as you're saying, like just plain baseline hyperlipidemia that's not cardiovascular disease, right?
• 21:27
  Rebecca Berens MD: Yeah.
• 21:27
  Rebecca Berens MD: So that's important distinction.
• 21:29
  Rebecca Berens MD: 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.
• 21:39
  Rebecca Berens MD: And there was a more marked effect seen in patients who had a higher BMI.
• 21:44
  Rebecca Berens MD: But that was, I will say that that was not necessarily one of the conditions that was required for being in the study.
• 21:52
  Rebecca Berens MD: Some of the BA patients had BMI criteria applied, some did not.
• 21:55
  Rebecca Berens MD: And then there was, variation noted in this study of the effectiveness and safety of various different GLP ones.
• 22:02
  Rebecca Berens MD: Because this was not just on semaglutide or tirzepatide.
• 22:05
  Rebecca Berens MD: This was including lide, liraglutide, exenatide, semaglutide.
• 22:09
  Rebecca Berens MD: Okay.
• 22:09
  Rebecca Berens MD: All the different ones.
• 22:10
  Rebecca Berens MD: 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.
• 22:23
  Rebecca Berens MD: 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.
• 22:37
  Rebecca Berens MD: 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.
• 22:48
  Rebecca Berens MD: So I wanted to make that clear for this study.
• 22:51
  Sonia Singh MD: So what you're saying is this sample included patients of a wide range of bmi?
• 22:57
  Sonia Singh MD: Not only patients with a certain who correct.
• 23:00
  Sonia Singh MD: BMI
• 23:00
  Rebecca Berens MD: criteria.
• 23:00
  Rebecca Berens MD: Correct.
• 23:00
  Rebecca Berens MD: And it did not include people who had a high BMI but did not already have a high risk diagnosis.
• 23:05
  Rebecca Berens MD: So BMI alone,
• 23:07
  Sonia Singh MD: right.
• 23:08
  Rebecca Berens MD: Is not the study population.
• 23:10
  Sonia Singh MD: Okay.
• 23:11
  Sonia Singh MD: 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.
• 23:26
  Rebecca Berens MD: Correct?
• 23:26
  Rebecca Berens MD: Correct.
• 23:27
  Sonia Singh MD: Okay, got it.
• 23:28
  Rebecca Berens MD: The next one I wanna talk about is cardiovascular and kidney outcomes.
• 23:32
  Rebecca Berens MD: 'cause I think this is another big discussion that happens is the benefits for not just cardiovascular disease, but also chronic kidney disease.
• 23:38
  Rebecca Berens MD: Related to diabetes.
• 23:41
  Rebecca Berens MD: Because that is one of the separate indications for adding a GLP one.
• 23:45
  Rebecca Berens MD: 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.
• 23:55
  Rebecca Berens MD: And so this was a systematic review and meta-analysis of randomized placebo controlled cardiovascular and kidney outcomes trials.
• 24:03
  Rebecca Berens MD: And it was looking across 10 trials and the long acting.
• 24:07
  Rebecca Berens MD: This was specifically the long acting GLP ones.
• 24:10
  Rebecca Berens MD: So that's like the, semaglutide and tirzepatide reduced the incidence of major adverse cardiovascular events.
• 24:17
  Rebecca Berens MD: So that's things like heart attacks and and like serious heart heart outcomes and the composite kidney outcome and all cause mortality.
• 24:25
  Rebecca Berens MD: And there was consistent 14% reduction for all of these components.
• 24:29
  Rebecca Berens MD: And there was no significant difference whether it was given by injection versus orally.
• 24:34
  Sonia Singh MD: Okay.
• 24:36
  Rebecca Berens MD: And again, these are all in patients with diabetes.
• 24:38
  Rebecca Berens MD: So to be clear, this is not just random patients with A BMI over 30 or patients who don't have diabetes.
• 24:44
  Rebecca Berens MD: 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.
• 24:52
  Sonia Singh MD: Okay.
• 24:53
  Rebecca Berens MD: 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.
• 25:01
  Rebecca Berens MD: And yet we are also using these medications to help with kidney benefits.
• 25:06
  Rebecca Berens MD: So that can be confusing for people.
• 25:07
  Rebecca Berens MD: 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.
• 25:16
  Rebecca Berens MD: Yeah.
• 25:16
  Rebecca Berens MD: If the patient is not intaking enough fluid or is having diarrhea as a side effect.
• 25:20
  Rebecca Berens MD: So we'll get more into side effects later, but just to be clear, these are different things that we're talking about?
• 25:23
  Rebecca Berens MD: Yes,
• 25:24
  Sonia Singh MD: Yes.
• 25:25
  Rebecca Berens MD: So the next benefit that I wanna talk about is metabolic associated STO liver disease or metabolic associated s STO hepatitis.
• 25:33
  Rebecca Berens MD: And so this means basically fatty liver is the colloquial name for this condition.
• 25:38
  Rebecca Berens MD: 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.
• 25:49
  Rebecca Berens MD: So this is a significant condition.
• 25:51
  Sonia Singh MD: Is this the new name for non-alcoholic s hepatitis?
• 25:55
  Rebecca Berens MD: Is
• 25:55
  Sonia Singh MD: this under that umbrella?
• 25:56
  Rebecca Berens MD: Yes, this is the new name for non-alcoholic Seattle
• 25:58
  Sonia Singh MD: Hepatitis.
• 25:59
  Sonia Singh MD: Okay.
• 25:59
  Sonia Singh MD: You're teaching me something new.
• 26:00
  Sonia Singh MD: Thank you for the, thank you for the CME.
• 26:02
  Rebecca Berens MD: Yeah, no worries.
• 26:03
  Rebecca Berens MD: Yeah.
• 26:03
  Rebecca Berens MD: For the patients out there, I think a lot of people are now familiar with the term fatty liver.
• 26:07
  Rebecca Berens MD: Fatty
• 26:07
  Sonia Singh MD: liver.
• 26:07
  Sonia Singh MD: Yeah.
• 26:08
  Rebecca Berens MD: And and fatty liver is associated with metabolic health conditions, particularly insulin resistance.
• 26:13
  Rebecca Berens MD: It results in excessive fat deposits in the liver.
• 26:17
  Rebecca Berens MD: 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.
• 26:24
  Rebecca Berens MD: 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.
• 26:32
  Rebecca Berens MD: And so it's a serious condition that's worth
• 26:34
  Sonia Singh MD: and
• 26:34
  Rebecca Berens MD: it's fairly
• 26:35
  Sonia Singh MD: common.
• 26:35
  Rebecca Berens MD: Very common.
• 26:36
  Rebecca Berens MD: And I actually think more common, I have a whole soap book about this that we can go off on, on another day.
• 26:41
  Rebecca Berens MD: But I actually think dieting is a big reason that we have a lot of this nowadays compared to before.
• 26:45
  Rebecca Berens MD: Oh, that's
• 26:45
  Sonia Singh MD: fascinating.
• 26:46
  Sonia Singh MD: I definitely wanna hear more about that.
• 26:48
  Rebecca Berens MD: We need to put a pin in that and we'll have a whole other.
• 26:49
  Rebecca Berens MD: Oh my gosh.
• 26:50
  Rebecca Berens MD: I didn't, why?
• 26:51
  Rebecca Berens MD: I think chronic diet causes metabolic associated fatty liver, but anyway, so this study was looking at GLP ones for.
• 26:59
  Rebecca Berens MD: Specifically this indication, metabolic associated steato liver disease or steato hepatitis.
• 27:04
  Rebecca Berens MD: And this included 25 RCTs or randomized controlled trials.
• 27:08
  Rebecca Berens MD: 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%.
• 27:26
  Rebecca Berens MD: 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.
• 27:33
  Rebecca Berens MD: And it induced significant histological improvements, meaning like looking under the microscope at tissue, there was actual improvement in how the tissue appeared.
• 27:42
  Rebecca Berens MD: Hepatocellular ballooning and lobular inflammation, but not significantly improved fibrosis with the evidence for tirzepatide more robust than that for semaglutide and liraglutide.
• 27:51
  Rebecca Berens MD: It also significantly decreased liver enzymes including A-S-T-A-L-T and GGT compared with the control.
• 27:58
  Rebecca Berens MD: It improved liver stiffness and there were no adverse effects of adverse effects involving the liver observed.
• 28:05
  Rebecca Berens MD: All that to say there is benefit for patients who have steatohepatitis using these medications.
• 28:11
  Rebecca Berens MD: But again, this is not just any random person who has.
• 28:16
  Rebecca Berens MD: A high BMI, this is just people who specifically have this condition that are benefiting from,
• 28:21
  Sonia Singh MD: 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.
• 28:29
  Sonia Singh MD: Because one of the primary treatments, at least that I know of for Seattle Hepatitis is weight loss.
• 28:34
  Sonia Singh MD: 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.
• 28:42
  Sonia Singh MD: Okay.
• 28:43
  Rebecca Berens MD: So yeah.
• 28:44
  Rebecca Berens MD: So fat loss from the liver.
• 28:45
  Rebecca Berens MD: Yes.
• 28:46
  Rebecca Berens MD: Yes.
• 28:47
  Rebecca Berens MD: I, and I think this is where my whole soapbox comes from.
• 28:49
  Rebecca Berens MD: If you lose weight, gain weight, lose weight, gain weight, every time you do that, there's actually more fat gained in the liver.
• 28:56
  Rebecca Berens MD: 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.
• 29:13
  Rebecca Berens MD: I think the sustainable changes that we can make metabolically, like increasing fiber and exercising and, using medications when indicated can all be helpful.
• 29:23
  Rebecca Berens MD: But I think it's more so at a metabolic level affecting the liver than it is just dropping weight.
• 29:28
  Rebecca Berens MD: Because I always say this too, you could you could go get liposuction and you would lose some weight.
• 29:32
  Rebecca Berens MD: But that wouldn't change your metabolic outcome.
• 29:35
  Rebecca Berens MD: So it's not the weight that's the problem.
• 29:37
  Rebecca Berens MD: It's the how you lost the weight.
• 29:38
  Rebecca Berens MD: And so how you lost the weight.
• 29:40
  Rebecca Berens MD: It has more to do with your behaviors than it has to do with the actual pounds lost.
• 29:44
  Sonia Singh MD: Interesting.
• 29:46
  Sonia Singh MD: Okay.
• 29:46
  Sonia Singh MD: I am not familiar with all the deep data on this, so I will have to
• 29:50
  Rebecca Berens MD: reserve judgment.
• 29:50
  Sonia Singh MD: We
• 29:51
  Rebecca Berens MD: have to we need to do another episode just
• 29:52
  Sonia Singh MD: on Okay.
• 29:52
  Sonia Singh MD: We'll do another just
• 29:53
  Rebecca Berens MD: on national fatty liver.
• 29:54
  Sonia Singh MD: There's a lot of crazy stuff about fatty liver on, on social media too.
• 29:58
  Sonia Singh MD: Yeah.
• 29:58
  Sonia Singh MD: There's a few people that have made a buck or two with some fatty liver miracle treatments.
• 30:03
  Sonia Singh MD: Okay.
• 30:04
  Sonia Singh MD: Okay.
• 30:04
  Sonia Singh MD: So now tell us about the grand finale Weight loss.
• 30:07
  Sonia Singh MD: Okay.
• 30:07
  Sonia Singh MD: Tell us about weight loss.
• 30:09
  Rebecca Berens MD: Okay, so weight loss.
• 30:09
  Rebecca Berens MD: Is this a benefit?
• 30:11
  Rebecca Berens MD: I don't know.
• 30:11
  Rebecca Berens MD: I
• 30:14
  Sonia Singh MD: Oh, interesting take you're starting with.
• 30:15
  Sonia Singh MD: Okay.
• 30:16
  Sonia Singh MD: Yeah.
• 30:16
  Rebecca Berens MD: Yeah.
• 30:16
  Rebecca Berens MD: I think, so where we're talk, because we were talking about all the benefits, right?
• 30:19
  Rebecca Berens MD: What is the benefit of weight loss?
• 30:23
  Rebecca Berens MD: 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.
• 30:33
  Rebecca Berens MD: That's great.
• 30:34
  Rebecca Berens MD: But it could actually be for a really bad reason.
• 30:36
  Rebecca Berens MD: 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?
• 30:50
  Rebecca Berens MD: 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.
• 31:02
  Rebecca Berens MD: It's just a change in body weight.
• 31:03
  Rebecca Berens MD: Now, I think there are people who are struggling with mobility related issues that certainly can benefit when they lose weight.
• 31:12
  Rebecca Berens MD: Like maybe they're less pressure on arthritic joints or things that makes it easier for'em to move around.
• 31:17
  Rebecca Berens MD: There are things where the actual body weight change makes a difference.
• 31:22
  Rebecca Berens MD: But in terms of the actual health outcomes, I'm not so convinced that always has such a huge benefit.
• 31:27
  Rebecca Berens MD: But anyway, we'll get into the
• 31:29
  Sonia Singh MD: data here.
• 31:30
  Sonia Singh MD: 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?
• 31:36
  Sonia Singh MD: But.
• 31:37
  Sonia Singh MD: 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.
• 31:51
  Sonia Singh MD: And that is not the case for everybody.
• 31:53
  Sonia Singh MD: Plenty of people will still have to be on their blood pressure medicine and that will not change.
• 31:57
  Sonia Singh MD: And she also had high cholesterol and that did not change even with weight loss.
• 32:01
  Sonia Singh MD: 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.
• 32:16
  Sonia Singh MD: And even when her weight doesn't under control, the cholesterol does not change.
• 32:18
  Sonia Singh MD: But, so yeah, that will not be the case for everybody.
• 32:21
  Sonia Singh MD: But, sleep apnea, sleep ap, a lot of people no longer have sleep apnea after they have a significant weight loss.
• 32:27
  Sonia Singh MD: So I guess to me, I think the, I'm not saying that weight loss always in and of itself is good.
• 32:34
  Sonia Singh MD: There's certainly a way to lose weight in a very unhealthy way with or without GLP ones.
• 32:40
  Sonia Singh MD: But I think there are many benefits potentially beyond just the number changing on the scale or cosmetics or, whatever.
• 32:49
  Rebecca Berens MD: Yeah, I think Okay.
• 32:51
  Rebecca Berens MD: Blood pressure, for example, like yes, if you are at a higher body weight, the blood pressure generally does increase because there Yeah.
• 32:59
  Rebecca Berens MD: It's a physical change.
• 33:00
  Rebecca Berens MD: 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.
• 33:17
  Rebecca Berens MD: Who are metabolically very healthy, who follow good behaviors, but still would qualify by FDA approval to use one of these medications.
• 33:26
  Rebecca Berens MD: And I guess that's what I mean when I say is that really a benefit?
• 33:29
  Rebecca Berens MD: Because what, what are we treating?
• 33:31
  Rebecca Berens MD: We're, are we treating the weight or are we treating the metabolic problems?
• 33:35
  Rebecca Berens MD: 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?
• 33:49
  Rebecca Berens MD: Yes.
• 33:49
  Rebecca Berens MD: And so if we treat that issue and those conditions improve, that's great.
• 33:54
  Rebecca Berens MD: All, all good.
• 33:55
  Rebecca Berens MD: But if I have a patient who's otherwise doing really well but just their BMI is high, I, I struggle with the.
• 34:03
  Rebecca Berens MD: The ethics and the discussion about why would we medicate that?
• 34:07
  Rebecca Berens MD: And so that's the reason I say like, why is that a benefit?
• 34:10
  Rebecca Berens MD: And I think to me it's more so what are the actual observable metabolic health outcomes that matter.
• 34:16
  Rebecca Berens MD: And I don't see just weight loss as an outcome that actually matters.
• 34:21
  Sonia Singh MD: Okay.
• 34:21
  Sonia Singh MD: 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.
• 34:32
  Sonia Singh MD: It is the treatment of an underlying metabolic disorder or pathology, that is what's giving them the benefit.
• 34:41
  Sonia Singh MD: I think, no, no one is telling you that this has to be given.
• 34:44
  Sonia Singh MD: 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.
• 34:52
  Sonia Singh MD: I do what I wanna do.
• 34:53
  Sonia Singh MD: I get around, I don't have any issues with it.
• 34:56
  Sonia Singh MD: And they had no, other medical conditions that seemed to be.
• 35:00
  Sonia Singh MD: Exacerbated by their weight alone.
• 35:03
  Sonia Singh MD: I certainly would not be like you should be on this,
• 35:06
  Rebecca Berens MD: you wouldn't Sonia, but many doctors would.
• 35:09
  Sonia Singh MD: Yes, okay.
• 35:11
  Sonia Singh MD: 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.
• 35:26
  Sonia Singh MD: And I would really like to lose 20 pounds.
• 35:27
  Sonia Singh MD: And I've been trying to do it every other way and I just haven't been able to.
• 35:31
  Sonia Singh MD: And in that person I would absolutely talk to them about it.
• 35:34
  Sonia Singh MD: And that would be just the benefit of weight loss.
• 35:37
  Sonia Singh MD: But tell me what your thoughts on that would be.
• 35:39
  Rebecca Berens MD: 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?
• 35:49
  Rebecca Berens MD: They're uncomfortable in their body because of societal stigma tells them
• 35:53
  Sonia Singh MD: well,
• 35:54
  Rebecca Berens MD: I do.
• 35:54
  Rebecca Berens MD: 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.
• 36:05
  Rebecca Berens MD: Yeah.
• 36:05
  Sonia Singh MD: Right.
• 36:05
  Rebecca Berens MD: A lot of doctors would, and that would happen, right?
• 36:08
  Rebecca Berens MD: 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.
• 36:16
  Rebecca Berens MD: I've had patients who were at an exercise class exercising yes.
• 36:20
  Rebecca Berens MD: 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.
• 36:28
  Rebecca Berens MD: And it's I was literally exercising.
• 36:30
  Sonia Singh MD: Yes.
• 36:30
  Rebecca Berens MD: So that constant barrage of nagging is that, is creating discomfort and is also affecting the quality of their healthcare for no good reason.
• 36:42
  Sonia Singh MD: Yes, and I'm not, I am not denying at all that weight stigma exists.
• 36:47
  Sonia Singh MD: It for sure does.
• 36:49
  Sonia Singh MD: And I'm also acknowledging that probably my practice differs slightly.
• 36:53
  Sonia Singh MD: Like I don't even really have the weight conversation with somebody unless they bring it up.
• 36:57
  Sonia Singh MD: Or it comes up in some other way, I don't independently just say let's talk about your weight.
• 37:02
  Sonia Singh MD: I just never do that.
• 37:02
  Sonia Singh MD: I don't even, I ask people if they want to be weighed, yeah.
• 37:05
  Sonia Singh MD: 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.
• 37:20
  Sonia Singh MD: 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.
• 37:29
  Sonia Singh MD: And I've had this conversation so many times with people.
• 37:31
  Sonia Singh MD: So a lot of times in that case I'll say, okay, tell me a little bit more about what your goal is.
• 37:35
  Sonia Singh MD: What is the intention here?
• 37:36
  Sonia Singh MD: What is the goal?
• 37:37
  Sonia Singh MD: Where do you wanna get to and why?
• 37:38
  Sonia Singh MD: 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.
• 37:49
  Sonia Singh MD: 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.
• 37:59
  Sonia Singh MD: I don't wanna wait until I do have sleep apnea.
• 38:02
  Sonia Singh MD: I don't wanna wait until my knees do start hurting.
• 38:04
  Sonia Singh MD: If there's anything I can do to lower my cardiovascular risk long term, like I wanna do it now.
• 38:10
  Sonia Singh MD: 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.
• 38:16
  Sonia Singh MD: And sometimes it is just, I wanna feel better in my clothes.
• 38:20
  Sonia Singh MD: I don't feel like anything fits me right anymore since I've been at this suite.
• 38:23
  Sonia Singh MD: I just want, then it becomes that, which I hear what you're saying in that.
• 38:27
  Sonia Singh MD: If somebody who.
• 38:29
  Sonia Singh MD: Had a normal BMI said that to me.
• 38:32
  Sonia Singh MD: I may be more, moving towards acceptance of our money and yeah, medically this is not a problem.
• 38:38
  Sonia Singh MD: 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.
• 38:46
  Sonia Singh MD: 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.
• 38:51
  Sonia Singh MD: 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.
• 39:03
  Sonia Singh MD: And maybe if they're driving it too, then I can be on board with that.
• 39:09
  Sonia Singh MD: So I don't know.
• 39:09
  Sonia Singh MD: You I'm telling you what I think a lot of people are.
• 39:11
  Sonia Singh MD: Yeah.
• 39:11
  Sonia Singh MD: Hear what you're saying and say to you.
• 39:13
  Rebecca Berens MD: And I hear you and I, my answer to that would be the benefits and the risks for you at this moment.
• 39:21
  Rebecca Berens MD: What do we have on the benefits and risks for you at this moment?
• 39:25
  Rebecca Berens MD: Weight loss alone is the only benefit that we have right now.
• 39:30
  Rebecca Berens MD: If we don't have any other metabolic issues going on, right?
• 39:32
  Rebecca Berens MD: Sure.
• 39:33
  Rebecca Berens MD: If you have fatty liver, if you have high sleep apnea, these other things going on, that's a different conversation.
• 39:38
  Rebecca Berens MD: But if we have no other issues.
• 39:40
  Rebecca Berens MD: And it's just weight loss, is that a sufficient benefit to outweigh all the potential risks that we're gonna talk about?
• 39:46
  Rebecca Berens MD: 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.
• 39:55
  Rebecca Berens MD: And again, if there's medical, other things going on, it's different.
• 39:59
  Rebecca Berens MD: 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.
• 40:16
  Rebecca Berens MD: 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.
• 40:30
  Rebecca Berens MD: So that's my, okay.
• 40:32
  Rebecca Berens MD: We'll
• 40:32
  Sonia Singh MD: 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?
• 40:45
  Rebecca Berens MD: So I, I think the issue in that, in most of those cases is related to metabolic dysfunction, hyperinsulinism.
• 40:53
  Sonia Singh MD: Okay.
• 40:54
  Sonia Singh MD: So you're saying in order to really get to the bottom of that, you would have to distinguish.
• 41:01
  Sonia Singh MD: 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.
• 41:11
  Sonia Singh MD: If it's still associated with it.
• 41:12
  Rebecca Berens MD: Yeah.
• 41:12
  Rebecca Berens MD: And I feel like that, ha, that's never done.
• 41:14
  Rebecca Berens MD: 'cause everyone just lumps them together.
• 41:16
  Rebecca Berens MD: And I don't think it's fair to do that.
• 41:18
  Rebecca Berens MD: And there's also people who have a quote, normal BMI, who have metabolic dysfunction.
• 41:22
  Sonia Singh MD: Of course,
• 41:23
  Rebecca Berens MD: yes.
• 41:23
  Rebecca Berens MD: Yes.
• 41:23
  Rebecca Berens MD: 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.
• 41:32
  Rebecca Berens MD: And I think it is something that we should all reflect on.
• 41:35
  Rebecca Berens MD: 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.
• 41:45
  Sonia Singh MD: Okay.
• 41:45
  Rebecca Berens MD: That's what we're gonna go,
• 41:46
  Sonia Singh MD: I'm gonna let you move on.
• 41:48
  Sonia Singh MD: Okay.
• 41:48
  Sonia Singh MD: Tell us about weight loss.
• 41:49
  Sonia Singh MD: Okay.
• 41:50
  Rebecca Berens MD: So
• 41:51
  Sonia Singh MD: I say quote unquote benefits,
• 41:54
  Rebecca Berens MD: Quote unquote.
• 41:54
  Rebecca Berens MD: Okay.
• 41:55
  Rebecca Berens MD: This study efficacy and safety of glucagon light peptide receptor agonists for weight loss among adults without diabetes.
• 42:03
  Rebecca Berens MD: Okay.
• 42:04
  Rebecca Berens MD: So this is the big systematic review.
• 42:07
  Rebecca Berens MD: So this is reviewing a total of 26 randomized controlled trials over 15,000 participants.
• 42:14
  Rebecca Berens MD: And it included 12 agents, three commercially available agents, and nine pre-market agents.
• 42:20
  Rebecca Berens MD: Treatment ranged from 16 to 104 weeks with a median of 43 weeks.
• 42:25
  Rebecca Berens MD: So that's less than a year also, which is important to know.
• 42:28
  Rebecca Berens MD: Tirzepatide, liraglutide RERA tach ide and semaglutide all resulted in weight loss.
• 42:34
  Rebecca Berens MD: Tirzepatide was up to 17.8%, semaglutide 13.9%, liraglutide 5.8%, and reride 24.9% after 48 weeks.
• 42:45
  Rebecca Berens MD: And so there were varying degrees of efficacy, but all resulted in significant weight loss.
• 42:51
  Rebecca Berens MD: Adverse effects were frequent, but the majority of which were GI related, nausea, vomiting, diarrhea, and constipation.
• 42:56
  Rebecca Berens MD: But.
• 42:58
  Rebecca Berens MD: Adverse effects that were severe enough to actually stop taking the medication.
• 43:01
  Rebecca Berens MD: Were pretty rare.
• 43:03
  Rebecca Berens MD: And
• 43:04
  Sonia Singh MD: so
• 43:04
  Rebecca Berens MD: that and
• 43:04
  Sonia Singh MD: serious adverse events were even rarer
• 43:07
  Rebecca Berens MD: Yeah.
• 43:07
  Rebecca Berens MD: Yeah.
• 43:08
  Rebecca Berens MD: As, yeah.
• 43:08
  Rebecca Berens MD: Severe adverse events were even, were also rare.
• 43:10
  Sonia Singh MD: 24.9% weight loss is insane.
• 43:13
  Sonia Singh MD: That is a lot of ways.
• 43:14
  Rebecca Berens MD: And so that's also my question is like, where is our line?
• 43:18
  Rebecca Berens MD: What is our goal?
• 43:20
  Rebecca Berens MD: Because I think a lot of people look at these studies and they're like, oh it makes you look great.
• 43:23
  Rebecca Berens MD: I'm like, yeah, but that's not universally good.
• 43:26
  Rebecca Berens MD: And there's at what point do we decide it's enough?
• 43:29
  Sonia Singh MD: Yeah.
• 43:30
  Sonia Singh MD: And I just wanna point out that, these are not the first weight loss drugs.
• 43:33
  Sonia Singh MD: There were weight loss drugs before this, there was fenden, many people will remember.
• 43:38
  Sonia Singh MD: Phentermine was one of those ingredients.
• 43:40
  Sonia Singh MD: There's orlistat, Lorrin Vic.
• 43:42
  Sonia Singh MD: There, Contrave, there were drugs before this, but nothing with this level of effectiveness.
• 43:50
  Sonia Singh MD: Yes.
• 43:50
  Sonia Singh MD: And tolerability.
• 43:51
  Sonia Singh MD: So this really is quite an advancement in this, category.
• 43:55
  Rebecca Berens MD: Yeah.
• 43:56
  Rebecca Berens MD: And a lots of those things were later pulled.
• 43:58
  Sonia Singh MD: Yes.
• 44:00
  Sonia Singh MD: They were.
• 44:00
  Rebecca Berens MD: So
• 44:00
  Sonia Singh MD: none of them were great.
• 44:01
  Sonia Singh MD: Hated all of them actually.
• 44:03
  Rebecca Berens MD: Yeah.
• 44:03
  Rebecca Berens MD: So the thing is I think.
• 44:06
  Rebecca Berens MD: There is weight loss with these medications, but I think we just have to assess what is the actual benefit of that.
• 44:11
  Rebecca Berens MD: Okay.
• 44:11
  Rebecca Berens MD: So then this one here this one is the an original WEGOVY trial.
• 44:16
  Rebecca Berens MD: So funded by Novo Nordisk once weekly semaglutide in adults with overweight or obesity.
• 44:20
  Rebecca Berens MD: And this is looking at the primary endpoints of weight loss.
• 44:25
  Rebecca Berens MD: It also looked at waist circumference change, systolic blood pressure, physical functioning score.
• 44:30
  Rebecca Berens MD: 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.
• 44:42
  Rebecca Berens MD: So I think that is a little bit more relevant.
• 44:45
  Rebecca Berens MD: Yeah.
• 44:45
  Rebecca Berens MD: 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.
• 44:59
  Rebecca Berens MD: And then for Tirzepatide,, there is a meta-analysis of nine randomized controlled trials containing over 7,000 participants.
• 45:05
  Rebecca Berens MD: They're mainly for middle and high co countries.
• 45:07
  Rebecca Berens MD: The main comparison was tirzepatide versus placebo.
• 45:10
  Rebecca Berens MD: But there was one that was Tirzepatide versus Semaglutide.
• 45:13
  Rebecca Berens MD: And it did include participants who had other medical comorbidities, not just high BMI.
• 45:17
  Rebecca Berens MD: And these included both medium term follow ups, most of them, which was about 12 to 18 months.
• 45:22
  Rebecca Berens MD: And one was long-term follow up at 3.5 years.
• 45:25
  Rebecca Berens MD: And there was evidence of weight loss at medium term followup and sustained weight loss at the longer term followup.
• 45:33
  Rebecca Berens MD: 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.
• 45:43
  Rebecca Berens MD: And again, this did include patients who had other risk factors, not just.
• 45:48
  Rebecca Berens MD: High BMI.
• 45:49
  Rebecca Berens MD: 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.
• 45:58
  Speaker 3: Right.
• 45:59
  Rebecca Berens MD: 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.
• 46:09
  Rebecca Berens MD: And that we are seeing sustained benefit because we do have evidence that not sustaining weight loss without sustaining it, is actually very harmful.
• 46:20
  Rebecca Berens MD: 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.
• 46:44
  Rebecca Berens MD: And so basically comparing someone who lose gain, versus someone who just stays at the high BMI, even if those BMIs are the same.
• 46:53
  Rebecca Berens MD: You actually do worse metabolically when you cycle than if you just stay there.
• 46:57
  Rebecca Berens MD: Yeah.
• 46:57
  Rebecca Berens MD: And that's what I think is really important and I think is not discussed enough.
• 47:01
  Rebecca Berens MD: Because if we're gonna put someone on a medication like this is considered to be a lifelong medication.
• 47:07
  Rebecca Berens MD: Yeah.
• 47:09
  Rebecca Berens MD: 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.
• 47:16
  Rebecca Berens MD: And so if you're gonna be treated for it, you're gonna be treated for it lifelong.
• 47:19
  Rebecca Berens MD: 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.
• 47:29
  Rebecca Berens MD: 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.
• 47:40
  Rebecca Berens MD: And this is a risk that I think is not discussed enough.
• 47:44
  Sonia Singh MD: Yeah.
• 47:45
  Sonia Singh MD: 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.
• 48:01
  Sonia Singh MD: 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.
• 48:05
  Sonia Singh MD: And nothing is happening.
• 48:06
  Sonia Singh MD: Like literally I've had people tell me I'm only eating 800 calories and I don't lose any weight.
• 48:10
  Sonia Singh MD: How can, how is that physiologically possible?
• 48:14
  Sonia Singh MD: 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.
• 48:26
  Sonia Singh MD: And.
• 48:27
  Sonia Singh MD: They're not healthy, yes.
• 48:28
  Sonia Singh MD: In any way.
• 48:30
  Sonia Singh MD: 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?
• 48:39
  Sonia Singh MD: That's one of the most common questions I get from patients.
• 48:42
  Sonia Singh MD: 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?
• 48:48
  Sonia Singh MD: 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.
• 48:58
  Sonia Singh MD: 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.
• 49:06
  Sonia Singh MD: 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.
• 49:14
  Sonia Singh MD: And we know that there's a lot of downstream bad health consequences of losing too much muscle mass and having sarcopenia.
• 49:20
  Sonia Singh MD: Yeah.
• 49:21
  Sonia Singh MD: Anyway, all, all important points that we need to talk about.
• 49:24
  Rebecca Berens MD: Yeah.
• 49:25
  Rebecca Berens MD: And then the last potential benefit that I'm gonna mention, and this is still early.
• 49:30
  Rebecca Berens MD: There is some animal and very early observational human data of reduced substance use behaviors with GLP ones.
• 49:38
  Rebecca Berens MD: 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.
• 49:47
  Rebecca Berens MD: And so it makes sense that there would be some interaction with substance use and potentially some other mental health conditions.
• 49:53
  Rebecca Berens MD: But this needs a lot more further study.
• 49:54
  Rebecca Berens MD: This is not something where we're like ready to claim anything about, clear benefits with the GLP ones for
• 50:01
  Sonia Singh MD: research.
• 50:01
  Sonia Singh MD: So as of now, the FDA approved indications are really diabetes, obesity, and sleep apnea are the ones that I think are official.
• 50:11
  Rebecca Berens MD: Yeah.
• 50:11
  Rebecca Berens MD: And then and fatty liver disease and kidney disease, but again, in people with diabetes,
• 50:16
  Sonia Singh MD: in people with diabetes.
• 50:17
  Sonia Singh MD: Yeah.
• 50:17
  Sonia Singh MD: Okay.
• 50:17
  Sonia Singh MD: Yeah.
• 50:17
  Sonia Singh MD: Okay.
• 50:18
  Sonia Singh MD: Okay, so now let's talk a little bit more about risks and side effects.
• 50:23
  Rebecca Berens MD: Yeah.
• 50:23
  Rebecca Berens MD: Most common and clearly documented and definitely these are real side effects is GI side effects.
• 50:29
  Rebecca Berens MD: And the most common ones are mild.
• 50:31
  Rebecca Berens MD: So like nausea, upset, stomach, heartburn, constipation, sometimes diarrhea, usually mild.
• 50:38
  Rebecca Berens MD: Usually adjust within a couple of weeks and then diminish over time.
• 50:42
  Rebecca Berens MD: And then become more tolerable.
• 50:44
  Rebecca Berens MD: Gallbladder events, meaning like gallstones and and biliary colic that that can be increased also.
• 50:51
  Rebecca Berens MD: And that could be potentially more serious because gallstones can cause pancreatitis, in some cases they can cause infections.
• 50:59
  Rebecca Berens MD: There, there can be more serious side effects, related to gallstones, but those are also less common.
• 51:05
  Rebecca Berens MD: And these are dose dependent side effects.
• 51:08
  Rebecca Berens MD: 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.
• 51:21
  Rebecca Berens MD: And the most common ones are those more mild and adjustable yeah, side effects.
• 51:26
  Rebecca Berens MD: And then as you mentioned, the loss of lean mass is another big concern that people have with side effects.
• 51:31
  Rebecca Berens MD: 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.
• 51:44
  Rebecca Berens MD: And they have guidelines about how to reviewing a variety of studies and how to minimize this effect on sarcopenia.
• 51:52
  Rebecca Berens MD: 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.
• 52:04
  Rebecca Berens MD: Yeah.
• 52:04
  Rebecca Berens MD: But exercise is something that can mitigate some of that risk.
• 52:09
  Rebecca Berens MD: 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.
• 52:19
  Rebecca Berens MD: 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.
• 52:29
  Rebecca Berens MD: Ooh.
• 52:29
  Rebecca Berens MD: Yeah.
• 52:29
  Sonia Singh MD: Real low.
• 52:30
  Sonia Singh MD: Okay.
• 52:31
  Rebecca Berens MD: Horrible.
• 52:31
  Rebecca Berens MD: Participants were randomized to one of four groups for 52 weeks, and so they all did the 800 calorie calories a day diet.
• 52:38
  Rebecca Berens MD: And then they went to one of four groups.
• 52:40
  Rebecca Berens MD: 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.
• 52:50
  Rebecca Berens MD: So all did 800.
• 52:51
  Rebecca Berens MD: And did
• 52:52
  Sonia Singh MD: they continue the 800 calorie diet?
• 52:53
  Sonia Singh MD: No.
• 52:54
  Sonia Singh MD: Oh, okay.
• 52:55
  Rebecca Berens MD: Okay.
• 52:55
  Rebecca Berens MD: Yeah.
• 52:55
  Rebecca Berens MD: So they all did the 800 hundred calorie diet in initially, and then they all went to these other forearms.
• 53:01
  Sonia Singh MD: Okay.
• 53:01
  Rebecca Berens MD: And they all did of course have lean mass loss.
• 53:05
  Rebecca Berens MD: But in the combination group, meaning GLP one plus exercise, the bone mineral density was unchanged with placebo at the hip and lumbar spine.
• 53:15
  Rebecca Berens MD: 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.
• 53:27
  Sonia Singh MD: So basically the idea is that as long as you're doing exercise with the GLP one, it cancels out Yes.
• 53:32
  Sonia Singh MD: Perhaps the bone density loss
• 53:34
  Rebecca Berens MD: that it has.
• 53:34
  Rebecca Berens MD: 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.
• 53:45
  Sonia Singh MD: Right.
• 53:45
  Rebecca Berens MD: So these
• 53:46
  Sonia Singh MD: effect the law, the effect on bone loss can be mitigated somewhat with exercise.
• 53:49
  Rebecca Berens MD: Yes.
• 53:50
  Sonia Singh MD: 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.
• 53:55
  Sonia Singh MD: Everyone's just gonna lose all this muscle mass.
• 53:57
  Sonia Singh MD: 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.
• 54:04
  Sonia Singh MD: It's gotta be done with, the exercise or weight training piece of it in order to maintain that and the bone density.
• 54:10
  Sonia Singh MD: Yeah.
• 54:11
  Sonia Singh MD: Okay.
• 54:11
  Sonia Singh MD: Go on.
• 54:12
  Rebecca Berens MD: And then a couple other side effects that I hear a lot about that are actually less concerning than people worry about.
• 54:16
  Rebecca Berens MD: So one is I think people have heard a lot about these eye side effects.
• 54:19
  Rebecca Berens MD: Yeah.
• 54:20
  Rebecca Berens MD: And so this is actually primarily in people who have diabetes and have preexisting retinopathy or retinal blood vessel disease.
• 54:28
  Rebecca Berens MD: 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.
• 54:35
  Rebecca Berens MD: So this is more of an effect of the rapid lowering of blood.
• 54:37
  Rebecca Berens MD: Yeah.
• 54:38
  Rebecca Berens MD: Sugar affecting the retinopathy than it is a direct effect of the drug.
• 54:41
  Rebecca Berens MD: So less of a concern than I think it is made out to be.
• 54:44
  Rebecca Berens MD: The other one is cancer risk.
• 54:46
  Rebecca Berens MD: 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.
• 54:58
  Rebecca Berens MD: You cannot use this medication.
• 55:00
  Rebecca Berens MD: This is based on some, in some animal studies where in rodents there was a risk for inducing C cell tumors in the thyroid.
• 55:10
  Rebecca Berens MD: 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.
• 55:20
  Rebecca Berens MD: And and they were also using much higher doses in rodents.
• 55:23
  Rebecca Berens MD: So we don't think this risk really applies that much to to humans.
• 55:27
  Rebecca Berens MD: 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.
• 55:34
  Yeah.
• 55:34
  Rebecca Berens MD: And there was a study looking at cancers in general GLP one receptor agonists and cancer risk in adults with obesity.
• 55:41
  Rebecca Berens MD: And it compared the incidence of 14 cancers among adults with obesity prescribed GLP ones versus non-users.
• 55:47
  Rebecca Berens MD: It was a retrospective cohort study and it was using EHR data from 2014 to 2024.
• 55:53
  Rebecca Berens MD: 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.
• 56:08
  Rebecca Berens MD: 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.
• 56:20
  Rebecca Berens MD: So for endometrial cancer for example, that's one that we know is metabolically associated ovarian cancer and meningioma.
• 56:26
  Rebecca Berens MD: There was the only one there where there was a slightly increased risk, but it was a not significant increase.
• 56:31
  Rebecca Berens MD: Was kidney cancer Again, slight increase, not considered statistically significant, but.
• 56:37
  Rebecca Berens MD: A signal worth, paying attention to.
• 56:39
  Rebecca Berens MD: Yeah.
• 56:39
  Rebecca Berens MD: And further follow up.
• 56:40
  Rebecca Berens MD: But again, there wasn't any indication of increased cancer of anything.
• 56:43
  Rebecca Berens MD: It was a decreased risk of cancer in patients with GLP ones.
• 56:46
  Sonia Singh MD: 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.
• 56:57
  Sonia Singh MD: Like this was just anybody who had a BMI over 30%?
• 57:00
  Rebecca Berens MD: Yes.
• 57:01
  Rebecca Berens MD: Yes.
• 57:01
  Sonia Singh MD: Yes.
• 57:01
  Sonia Singh MD: Okay.
• 57:02
  Sonia Singh MD: 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.
• 57:11
  Rebecca Berens MD: 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.
• 57:18
  Rebecca Berens MD: That's like a si, that's a symptom of their metabolic dysfunction, right?
• 57:21
  Rebecca Berens MD: 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.
• 57:28
  Rebecca Berens MD: So it's they co-occur, but they are not causal necessarily.
• 57:33
  Sonia Singh MD: Okay.
• 57:34
  Sonia Singh MD: Okay.
• 57:35
  Sonia Singh MD: The
• 57:35
  Rebecca Berens MD: cause and effect is going a different direction.
• 57:37
  Rebecca Berens MD: Is my,
• 57:39
  Sonia Singh MD: Okay.
• 57:40
  Sonia Singh MD: 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.
• 57:48
  Sonia Singh MD: 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.
• 57:57
  Rebecca Berens MD: Yeah.
• 57:57
  Rebecca Berens MD: 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.
• 58:07
  Rebecca Berens MD: 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.
• 58:15
  Rebecca Berens MD: 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.
• 58:31
  Rebecca Berens MD: And so I think that is something that that, that was shown in these pharmaco visualists as they were picking this up.
• 58:38
  Rebecca Berens MD: And since it doesn't appear to be a direct drug effect, because the subsequent meta-analysis ruled that out.
• 58:43
  Rebecca Berens MD: It's something to do with the population of people that was taking these medicines that made that pop up in the pharmacovigilance studies.
• 58:50
  Rebecca Berens MD: 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.
• 59:11
  Rebecca Berens MD: 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?
• 59:23
  Rebecca Berens MD: 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.
• 59:29
  Rebecca Berens MD: Yeah.
• 59:29
  Rebecca Berens MD: Which sounds very depressing.
• 59:31
  Sonia Singh MD: Yeah.
• 59:32
  Rebecca Berens MD: 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.
• 59:54
  Sonia Singh MD: Yeah.
• 59:54
  Sonia Singh MD: Honestly, I'm surprised that there's not more research or more just general talk around this topic.
• 1:00:00
  Sonia Singh MD: '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.
• 1:00:16
  Sonia Singh MD: I'm just surprised that there isn't more research on this topic.
• 1:00:18
  Sonia Singh MD: 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.
• 1:00:26
  Sonia Singh MD: And it feels like it's taken away this big.
• 1:00:28
  Sonia Singh MD: Joy in my life.
• 1:00:29
  Sonia Singh MD: And like another one who was like, I definitely feel like I get depressed when I take this medicine.
• 1:00:35
  Sonia Singh MD: It works, but I get very depressed and I don't wanna take it anymore.
• 1:00:38
  Sonia Singh MD: 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.
• 1:00:44
  Sonia Singh MD: But yeah, I'm curious to see what the future holds in terms of research in that area.
• 1:00:48
  Rebecca Berens MD: Yeah.
• 1:00:49
  Rebecca Berens MD: 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.
• 1:01:04
  Rebecca Berens MD: 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.
• 1:01:16
  Rebecca Berens MD: 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.
• 1:01:26
  Rebecca Berens MD: 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?
• 1:01:35
  Sonia Singh MD: Yeah.
• 1:01:35
  Rebecca Berens MD: And then the people that are taking them are, again, different than the people that were studied.
• 1:01:41
  Sonia Singh MD: Right.
• 1:01:41
  Rebecca Berens MD: And so it, it is really important not to apply.
• 1:01:45
  Rebecca Berens MD: The results of a study population that doesn't match you to yourself.
• 1:01:49
  Rebecca Berens MD: Yeah.
• 1:01:50
  Rebecca Berens MD: And
• 1:01:50
  Speaker 3: yeah,
• 1:01:51
  Rebecca Berens MD: 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.
• 1:02:05
  Rebecca Berens MD: And misusing them, having complications related to eating disorders.
• 1:02:10
  Rebecca Berens MD: And eating disorder is another one of the mental health side effects that is reported.
• 1:02:15
  Rebecca Berens MD: And was reported in this pharmacovigilance study.
• 1:02:18
  Rebecca Berens MD: There were significant signals for anxiety, mood disorders and suicidality and eating disorders with all three.
• 1:02:24
  Rebecca Berens MD: And the meta-analyses to remove this effect from, for depression and suicidality did not remove it for eating disorders.
• 1:02:34
  Rebecca Berens MD: It's not commented on.
• 1:02:36
  Sonia Singh MD: Interesting.
• 1:02:37
  Rebecca Berens MD: 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.
• 1:02:46
  Sonia Singh MD: Yeah.
• 1:02:46
  Rebecca Berens MD: I don't think most people are screening for it or asking the right questions.
• 1:02:49
  Sonia Singh MD: Yeah.
• 1:02:50
  Rebecca Berens MD: I don't think a lot of people are.
• 1:02:52
  Rebecca Berens MD: 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.
• 1:03:04
  Rebecca Berens MD: There's significant risk there and I think that may, that's a really important thing to be considering.
• 1:03:10
  Sonia Singh MD: Yeah.
• 1:03:10
  Sonia Singh MD: 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.
• 1:03:36
  Sonia Singh MD: I've heard stories of people sharing it with their friends and family and they're those people feeling awful.
• 1:03:42
  Sonia Singh MD: 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.
• 1:04:00
  Sonia Singh MD: They're just able to jump into it there.
• 1:04:02
  Sonia Singh MD: I think there was a whole article in the New Yorker or something about women DIYing their own weight loss regimens.
• 1:04:08
  Sonia Singh MD: And I think it's incredibly common and scary.
• 1:04:10
  Rebecca Berens MD: Yeah.
• 1:04:11
  Rebecca Berens MD: Yeah.
• 1:04:12
  Rebecca Berens MD: And then we,
• 1:04:13
  Sonia Singh MD: Let's talk a little bit about, I think you wanted talk a little bit about more about marketing and the cost associated
• 1:04:18
  Rebecca Berens MD: with it.
• 1:04:18
  Rebecca Berens MD: Yeah.
• 1:04:18
  Rebecca Berens MD: So I would consider the cost of risk, right?
• 1:04:20
  Rebecca Berens MD: Yeah.
• 1:04:20
  Rebecca Berens MD: 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.
• 1:04:33
  Rebecca Berens MD: And that's if you're using a cash pay discount.
• 1:04:35
  Rebecca Berens MD: 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.
• 1:04:43
  Rebecca Berens MD: Yeah.
• 1:04:43
  Rebecca Berens MD: Or they do quote unquote cover it, but they have to meet a deductible first.
• 1:04:47
  Rebecca Berens MD: So they have to pay$1,200 a month for three months for something before it's actually covered.
• 1:04:51
  Rebecca Berens MD: No, that's favorite.
• 1:04:52
  Rebecca Berens MD: 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.
• 1:05:09
  Sonia Singh MD: I see what you're saying.
• 1:05:12
  Sonia Singh MD: Yes, and I think that's a fair consideration.
• 1:05:15
  Sonia Singh MD: I guess what's popping up in my mind.
• 1:05:17
  Sonia Singh MD: Is.
• 1:05:17
  Sonia Singh MD: But what about the sustainability of just diet and exercise and lifestyle change?
• 1:05:22
  Sonia Singh MD: 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.
• 1:05:37
  Sonia Singh MD: It is an intervention with actually surprisingly low rates of long-term success.
• 1:05:42
  Sonia Singh MD: So I guess my question would be how do you think the sustainability compares?
• 1:05:47
  Sonia Singh MD: I don't know if we have the data to answer that, but what do you think?
• 1:05:49
  Rebecca Berens MD: Yeah, no, so you're right there.
• 1:05:50
  Rebecca Berens MD: 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.
• 1:05:59
  Rebecca Berens MD: 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.
• 1:06:05
  Rebecca Berens MD: I'm like you can't sustainably do that safely.
• 1:06:08
  Rebecca Berens MD: But so yeah, that, that is an issue.
• 1:06:09
  Rebecca Berens MD: And I think this is where we are weighing risks and benefits, right?
• 1:06:13
  Rebecca Berens MD: 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.
• 1:06:27
  Sonia Singh MD: Okay.
• 1:06:27
  Rebecca Berens MD: 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.
• 1:06:37
  Rebecca Berens MD: 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.
• 1:06:51
  Rebecca Berens MD: 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.
• 1:06:59
  Rebecca Berens MD: Are you talking
• 1:06:59
  Sonia Singh MD: about things like metformin?
• 1:07:00
  Rebecca Berens MD: Yeah, so I do use Metformin a lot and I think Metformin is really for now.
• 1:07:05
  Rebecca Berens MD: A really good option because it's cheap and easy to access and very well tolerated for the most part.
• 1:07:12
  Rebecca Berens MD: 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.
• 1:07:19
  Rebecca Berens MD: And coming on and off of this might actually be worse for you than something that you can sustain long term.
• 1:07:25
  Rebecca Berens MD: So if a GLP one is not sustainable for you long term, maybe metformin is something we should start with.
• 1:07:30
  Rebecca Berens MD: And see how we do with that, right?
• 1:07:31
  Rebecca Berens MD: So I think that's the, that's my main issue is just considering all of the risks and benefits of that.
• 1:07:36
  Rebecca Berens MD: And I don't think that the right call is just, everyone should go on these and then, yeah, okay.
• 1:07:41
  Rebecca Berens MD: Two years down the line, I don't have$500 a month anymore to keep paying for this.
• 1:07:45
  Rebecca Berens MD: Yeah.
• 1:07:45
  Rebecca Berens MD: Or, whatever else has happened and I, for whatever reason, I have to stop it and now we're in a different spot.
• 1:07:50
  Rebecca Berens MD: Yeah.
• 1:07:50
  Rebecca Berens MD: So I just, I think it's part of the conversation that I think is.
• 1:07:54
  Rebecca Berens MD: Is lacking, generally speaking.
• 1:07:56
  Sonia Singh MD: 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.
• 1:08:08
  Sonia Singh MD: 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.
• 1:08:18
  Sonia Singh MD: Or I just got, like I got lazy, or I whatever.
• 1:08:21
  Sonia Singh MD: Which I always correct them and I don't think that's the case at all.
• 1:08:24
  Sonia Singh MD: 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.
• 1:08:36
  Sonia Singh MD: And so all of those changes are then making it harder and harder for them to remain restricted in whatever way they're restricting.
• 1:08:43
  Sonia Singh MD: And so suddenly they'll start being like, huh, I don't, I started having intrusive thoughts about eating a donut.
• 1:08:48
  Sonia Singh MD: I don't even like donuts.
• 1:08:49
  Sonia Singh MD: 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.
• 1:08:57
  Sonia Singh MD: And I just, I don't think that is the case at all.
• 1:08:59
  Sonia Singh MD: I think there is a very complex per, set of metabolic processes that are driving that.
• 1:09:04
  Sonia Singh MD: 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.
• 1:09:10
  Sonia Singh MD: I gotta get this under control.
• 1:09:12
  Sonia Singh MD: And then they'll go back down.
• 1:09:13
  Sonia Singh MD: 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.
• 1:09:24
  Sonia Singh MD: 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.
• 1:09:35
  Sonia Singh MD: 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.
• 1:09:44
  Sonia Singh MD: That's very unlikely.
• 1:09:45
  Sonia Singh MD: Or bariatric surgery.
• 1:09:46
  Sonia Singh MD: 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.
• 1:09:59
  Sonia Singh MD: And you can gradually stretch it out with time and, gain back the weight.
• 1:10:01
  Sonia Singh MD: 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.
• 1:10:08
  Sonia Singh MD: So always make that point with people about GLP ones.
• 1:10:11
  Sonia Singh MD: Yeah.
• 1:10:11
  Sonia Singh MD: 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.
• 1:10:18
  Sonia Singh MD: 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.
• 1:10:38
  Sonia Singh MD: That's something that I think about often with people when I'm talking to'em about these meds.
• 1:10:42
  Rebecca Berens MD: Yeah.
• 1:10:42
  Rebecca Berens MD: 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.
• 1:10:49
  Rebecca Berens MD: What were we treating?
• 1:10:51
  Rebecca Berens MD: If you did have metabolic issues to begin with, then yeah.
• 1:10:54
  Rebecca Berens MD: I think that this is a great way of managing that.
• 1:10:57
  Rebecca Berens MD: But like even still, you still have to do we talked about the bone density.
• 1:11:00
  Rebecca Berens MD: You still have to do the exercise to maintain
• 1:11:03
  Sonia Singh MD: Yes.
• 1:11:03
  Rebecca Berens MD: Your bone density and your muscle mass.
• 1:11:04
  Rebecca Berens MD: You still have to get all of your macronutrients and micronutrients.
• 1:11:07
  Rebecca Berens MD: Yes.
• 1:11:07
  Rebecca Berens MD: We didn't even get into all of the risks of undereating that can happen Yes.
• 1:11:11
  Rebecca Berens MD: When you don't have any hunger cues and Yes.
• 1:11:13
  Rebecca Berens MD: The, significant nutritional deficiencies that you could have happen.
• 1:11:17
  Rebecca Berens MD: You have to fully weigh the risk amendments and I just think that this is a risk that is just not discussed enough.
• 1:11:25
  Rebecca Berens MD: And so I think, it, you have to, from where the person is starting, you have to be looking at the big picture.
• 1:11:31
  Rebecca Berens MD: What is their current metabolic health status?
• 1:11:34
  Rebecca Berens MD: What is, what are the potential risks of us doing this intervention?
• 1:11:38
  Rebecca Berens MD: '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.
• 1:11:43
  Rebecca Berens MD: Does it, is there actually data that shows that it's better to intervene on this early?
• 1:11:48
  Rebecca Berens MD: I would argue that data actually says the opposite.
• 1:11:51
  Rebecca Berens MD: Because when we start intervening early and we cycle, we make it worse.
• 1:11:54
  Rebecca Berens MD: So I would argue it's actually better to wait until there's sign of a problem before we start putting you on stuff.
• 1:11:59
  Rebecca Berens MD: But I think it is also a patient autonomy.
• 1:12:04
  Rebecca Berens MD: Discussion as well.
• 1:12:05
  Rebecca Berens MD: Because if a patient, knows their family history and they're like, I have all this stuff in my family.
• 1:12:10
  Rebecca Berens MD: I don't wanna go through what my family did.
• 1:12:11
  Rebecca Berens MD: I know genetically speaking, this is high likelihood for me, and this is something I struggle with.
• 1:12:16
  Rebecca Berens MD: Yeah, I think that's a different conversation, but again, it's the sustainability that, that really matters.
• 1:12:22
  Rebecca Berens MD: And so I just think it's an important consideration to have.
• 1:12:25
  Rebecca Berens MD: 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.
• 1:12:34
  Rebecca Berens MD: 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.
• 1:12:39
  Rebecca Berens MD: And to your point about the metabolic changes and the biological drivers of of, of this these changes.
• 1:12:46
  Rebecca Berens MD: I think if anything, what these drugs have taught us is how biological our drives are.
• 1:12:52
  Rebecca Berens MD: Our hunger.
• 1:12:52
  Rebecca Berens MD: Yes.
• 1:12:52
  Rebecca Berens MD: Our satiation, our cravings.
• 1:12:54
  Rebecca Berens MD: It is still fascinating to me when I see people say, it's just don't pick up the fork.
• 1:13:02
  Rebecca Berens MD: It's just willpower.
• 1:13:02
  Rebecca Berens MD: I'm like, yes.
• 1:13:04
  Rebecca Berens MD: This literally, you put this in and your brain just tells you something different.
• 1:13:08
  Sonia Singh MD: Yes.
• 1:13:08
  Rebecca Berens MD: That shows you how much this is biological, right?
• 1:13:10
  Rebecca Berens MD: Yes.
• 1:13:10
  Rebecca Berens MD: 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.
• 1:13:15
  Rebecca Berens MD: We think we have a lot of control over how we behave, and we actually do not.
• 1:13:20
  Rebecca Berens MD: Yeah.
• 1:13:20
  Rebecca Berens MD: And so I just think we should be cautious, is all I'm saying.
• 1:13:25
  Rebecca Berens MD: Yeah.
• 1:13:25
  Rebecca Berens MD: 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.
• 1:13:34
  Rebecca Berens MD: 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.
• 1:13:44
  Rebecca Berens MD: Driving us.
• 1:13:45
  Rebecca Berens MD: 'Cause we would follow different behaviors if our environment was set up differently.
• 1:13:49
  Sonia Singh MD: Yeah, absolutely.
• 1:13:50
  Sonia Singh MD: Yeah.
• 1:13:50
  Rebecca Berens MD: 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.
• 1:14:04
  Rebecca Berens MD: 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.
• 1:14:12
  Rebecca Berens MD: But why are we fixing them this way?
• 1:14:15
  Sonia Singh MD: 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.
• 1:14:22
  Sonia Singh MD: '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.
• 1:14:29
  Sonia Singh MD: And so I did a lot of the CME in preparation for that.
• 1:14:32
  Sonia Singh MD: Never ended up taking the test and doing it.
• 1:14:34
  Sonia Singh MD: 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.
• 1:14:45
  Sonia Singh MD: But there was a real big emphasis on use them liberally.
• 1:14:49
  Sonia Singh MD: 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.
• 1:14:59
  Sonia Singh MD: And this was 10 years ago.
• 1:15:00
  Sonia Singh MD: 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.
• 1:15:09
  Sonia Singh MD: 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.
• 1:15:20
  Sonia Singh MD: And I guess I don't know that we have really proven that one way or another.
• 1:15:23
  Sonia Singh MD: I don't know that there's data on that.
• 1:15:25
  Rebecca Berens MD: Yeah, I just think that Both the, the weight cycling data that's out there.
• 1:15:29
  Sonia Singh MD: Yeah.
• 1:15:30
  Rebecca Berens MD: 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.
• 1:15:41
  Rebecca Berens MD: And I think that I am not against the use of this tool.
• 1:15:45
  Rebecca Berens MD: I, I wanna be very clear about that.
• 1:15:47
  Rebecca Berens MD: I think that GLP ones are a wonderful tool for the right patient.
• 1:15:51
  Rebecca Berens MD: I just think we have to be counseling appropriately and we have to be monitoring appropriately.
• 1:15:55
  Rebecca Berens MD: And I think that is the part that is often not happening.
• 1:15:58
  Rebecca Berens MD: 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.
• 1:16:08
  Rebecca Berens MD: I think it's just, really important that we're being very clear about what the data does and doesn't show.
• 1:16:14
  Rebecca Berens MD: 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.
• 1:16:24
  Sonia Singh MD: I totally agree with you.
• 1:16:25
  Sonia Singh MD: 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.
• 1:16:34
  Sonia Singh MD: 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.
• 1:16:50
  Sonia Singh MD: We've talked about this for over an hour at this point.
• 1:16:53
  Sonia Singh MD: Imagine what fraction of that can possibly be communicated in an office visit.
• 1:16:56
  Rebecca Berens MD: Yeah,
• 1:16:57
  Sonia Singh MD: hard.
• 1:16:58
  Sonia Singh MD: Okay.
• 1:16:58
  Sonia Singh MD: 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.
• 1:17:10
  Rebecca Berens MD: Yeah, so I just wanted to bring that up as another risk to consider because of course there are FDA approved.
• 1:17:17
  Rebecca Berens MD: Versions of these drugs available direct from the manufacturer and through retail pharmacies, but they are expensive.
• 1:17:23
  Rebecca Berens MD: 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.
• 1:17:31
  Rebecca Berens MD: 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.
• 1:17:39
  Rebecca Berens MD: They just didn't have it in stock and they hadn't set up their direct to consumer sales yet.
• 1:17:43
  Rebecca Berens MD: So there was just no other way for people to get it.
• 1:17:45
  Rebecca Berens MD: So this is how they were getting it.
• 1:17:46
  Rebecca Berens MD: 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.
• 1:18:00
  Rebecca Berens MD: In some cases, the compounding pharmacies identified on the labels of the products do not exist.
• 1:18:03
  Rebecca Berens MD: 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.
• 1:18:12
  Rebecca Berens MD: So some of them are just frankly fraudulent, not even,
• 1:18:15
  Sonia Singh MD: yeah.
• 1:18:16
  Rebecca Berens MD: What they say, they are not made by who they say they are.
• 1:18:18
  Rebecca Berens MD: Compounded drugs in general, pharmacies are taking the ingredient.
• 1:18:22
  Rebecca Berens MD: For the medication and making it themselves because the formulation from the manufacturer is not available.
• 1:18:28
  Rebecca Berens MD: That's usually the time when compounds are produced.
• 1:18:31
  Rebecca Berens MD: And so during the shortages, that's when this really blossomed.
• 1:18:34
  Rebecca Berens MD: But it's also like where are they sourcing it from?
• 1:18:36
  Rebecca Berens MD: Often, not very clear.
• 1:18:38
  Rebecca Berens MD: 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.
• 1:18:48
  Rebecca Berens MD: And I got very unsatisfying answers, as you can imagine.
• 1:18:51
  Rebecca Berens MD: 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?
• 1:18:58
  Sonia Singh MD: Yeah.
• 1:18:59
  Rebecca Berens MD: So that, that was a big concern that I had.
• 1:19:01
  Rebecca Berens MD: The other concern with compounds is there is I important storage requirements for these medications.
• 1:19:08
  Rebecca Berens MD: They require refrigeration for the injectables, for example.
• 1:19:11
  Rebecca Berens MD: And so that there, if there are, compounded products that haven't been stored correctly.
• 1:19:16
  Rebecca Berens MD: There's just less regulation of that process.
• 1:19:18
  Rebecca Berens MD: Yeah.
• 1:19:18
  Rebecca Berens MD: There could be impact there on the efficacy and safety of those medications.
• 1:19:23
  Rebecca Berens MD: 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.
• 1:19:32
  Rebecca Berens MD: It's a salt form of the peptide.
• 1:19:33
  Rebecca Berens MD: Okay.
• 1:19:34
  Rebecca Berens MD: That is being used in compounds.
• 1:19:35
  Rebecca Berens MD: And this is not the exact same thing.
• 1:19:37
  Rebecca Berens MD: 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.
• 1:19:46
  Rebecca Berens MD: So that's really important to be aware of.
• 1:19:48
  Rebecca Berens MD: 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.
• 1:20:01
  Rebecca Berens MD: And so there may not be these reports of adverse events being given to the FDA.
• 1:20:06
  Rebecca Berens MD: 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.
• 1:20:17
  Rebecca Berens MD: 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.
• 1:20:30
  Rebecca Berens MD: Now where do you get it?
• 1:20:31
  Rebecca Berens MD: Yeah.
• 1:20:32
  Rebecca Berens MD: 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?
• 1:20:40
  Sonia Singh MD: 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.
• 1:20:46
  Sonia Singh MD: And by the way, FYI, you and I have no relationships with
• 1:20:50
  Rebecca Berens MD: no,
• 1:20:50
  Sonia Singh MD: Eli Lilly or any other pharmaceutical companies.
• 1:20:52
  Sonia Singh MD: So we're not financially motivated to make people take the brand name pharmaceutical in any way.
• 1:20:57
  Sonia Singh MD: But the analogy that I often use is knockoff handbags.
• 1:21:01
  Sonia Singh MD: So like a compounded mat is like a knockoff handbag.
• 1:21:04
  Sonia Singh MD: 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.
• 1:21:12
  Sonia Singh MD: 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.
• 1:21:18
  Sonia Singh MD: 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.
• 1:21:35
  Sonia Singh MD: 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.
• 1:21:48
  Sonia Singh MD: So I can understand why people, patients and consumers go to these options.
• 1:21:53
  Sonia Singh MD: But again, they need to be doing it with full understanding of the additional risk that they're taking on.
• 1:21:57
  Sonia Singh MD: So we talk a lot more about that in the peptide episode.
• 1:22:00
  Sonia Singh MD: 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.
• 1:22:10
  Sonia Singh MD: I think you really have to step back and be like whoa.
• 1:22:13
  Sonia Singh MD: How motivated are these people to ensure the quality and safety of this product?
• 1:22:17
  Sonia Singh MD: Are they calling and looking into the supply chain?
• 1:22:20
  Sonia Singh MD: I bet you they are not.
• 1:22:21
  Sonia Singh MD: This is where I think you really have to be a savvy consumer and think critically about.
• 1:22:26
  Sonia Singh MD: Where you're going for some of these products.
• 1:22:28
  Rebecca Berens MD: Yeah.
• 1:22:28
  Rebecca Berens MD: I love that analogy.
• 1:22:29
  Rebecca Berens MD: The knockoff handbag.
• 1:22:30
  Rebecca Berens MD: I'm gonna use
• 1:22:30
  Sonia Singh MD: that.
• 1:22:31
  Sonia Singh MD: Yeah.
• 1:22:31
  Sonia Singh MD: That's the one I use the most.
• 1:22:33
  Sonia Singh MD: So what can we learn from this as doctors and as humans?
• 1:22:37
  Rebecca Berens MD: 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.
• 1:22:49
  Rebecca Berens MD: And I think there is a lot of extrapolation of cardiovascular benefits to patients that were not in those cardiovascular studies.
• 1:22:58
  Sonia Singh MD: Yeah.
• 1:22:58
  Rebecca Berens MD: And the patients that were in just the weight loss studies, there was much less, but still some medical outcomes that were seen.
• 1:23:06
  Rebecca Berens MD: And so I just think we have to be very clear on what are the true risks that we know of?
• 1:23:11
  Rebecca Berens MD: What are the true benefits that we know of?
• 1:23:13
  Rebecca Berens MD: And for this patient in front of me, how do those weigh out?
• 1:23:18
  Rebecca Berens MD: And I think that's the key thing for me.
• 1:23:20
  Rebecca Berens MD: 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.
• 1:23:36
  Rebecca Berens MD: And neither one is wrong, but it has to be fully informed and I think that's what is often missing.
• 1:23:42
  Rebecca Berens MD: And I think as doctors.
• 1:23:44
  Rebecca Berens MD: We should be very thoughtful and cautious about using medications, any medication that influences a person's brain in particular.
• 1:23:55
  Rebecca Berens MD: 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.
• 1:24:10
  Sonia Singh MD: 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.
• 1:24:18
  Sonia Singh MD: 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.
• 1:24:37
  Sonia Singh MD: 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.
• 1:24:44
  Sonia Singh MD: Usually those are fairly straightforward to talk through.
• 1:24:47
  Sonia Singh MD: But the bigger barrier was this idea of but I should just be able to do this on my own.
• 1:24:52
  Sonia Singh MD: 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.
• 1:25:09
  Sonia Singh MD: It's not that simple.
• 1:25:10
  Sonia Singh MD: To boil it down to that is, is it's just not accurate.
• 1:25:14
  Sonia Singh MD: It's not true.
• 1:25:14
  Sonia Singh MD: 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.
• 1:25:32
  Sonia Singh MD: 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.
• 1:25:39
  Sonia Singh MD: It's an easy way out.
• 1:25:40
  Sonia Singh MD: 'cause I really think a lot of people.
• 1:25:43
  Sonia Singh MD: 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.
• 1:25:59
  Sonia Singh MD: 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.
• 1:26:07
  Sonia Singh MD: But obviously with a, careful selection, discussion of their values and priorities, understanding of the risks that it is long-term.
• 1:26:14
  Sonia Singh MD: All of those things.
• 1:26:15
  Rebecca Berens MD: Yeah.
• 1:26:16
  Rebecca Berens MD: 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.
• 1:26:22
  Rebecca Berens MD: And is no longer active.
• 1:26:24
  Rebecca Berens MD: Yeah.
• 1:26:24
  Rebecca Berens MD: 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.
• 1:26:31
  Sonia Singh MD: Yeah.
• 1:26:32
  Rebecca Berens MD: And they're fearful for that reason.
• 1:26:33
  Rebecca Berens MD: 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.
• 1:26:40
  Rebecca Berens MD: Yeah.
• 1:26:41
  Rebecca Berens MD: And I don't think that it's fair on either side.
• 1:26:46
  Rebecca Berens MD: 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.
• 1:26:52
  Rebecca Berens MD: And so now we're just not gonna treat your metabolic health problem.
• 1:26:54
  Rebecca Berens MD: That's not fair.
• 1:26:55
  Rebecca Berens MD: But it's also not fair to be like to.
• 1:26:58
  Rebecca Berens MD: You might get a metabolic health problem in the future because your BMI is this, so we should just give you this medicine now.
• 1:27:03
  Rebecca Berens MD: I also don't think that is,
• 1:27:05
  Sonia Singh MD: yeah.
• 1:27:05
  Rebecca Berens MD: Is it a thorough or appropriate approach?
• 1:27:07
  Rebecca Berens MD: 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.
• 1:27:14
  Rebecca Berens MD: It's the gold rush.
• 1:27:16
  Sonia Singh MD: Yeah.
• 1:27:16
  Rebecca Berens MD: And are they doing it thoughtfully?
• 1:27:19
  Rebecca Berens MD: Are you receiving care thoughtfully?
• 1:27:20
  Rebecca Berens MD: I think that is the important piece for a patient to be looking for.
• 1:27:26
  Rebecca Berens MD: 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.
• 1:27:33
  Rebecca Berens MD: Like for substance use, for example.
• 1:27:35
  Rebecca Berens MD: And other uses outside of metabolic health.
• 1:27:37
  Rebecca Berens MD: 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.
• 1:27:48
  Rebecca Berens MD: Because it's so difficult to parse out sometimes, especially if you don't have a lot of experience.
• 1:27:55
  Rebecca Berens MD: And is it binge eating because you were previously very restricted and this is actually normal
• 1:28:01
  Sonia Singh MD: right.
• 1:28:02
  Rebecca Berens MD: Eating to recover after a period of significant restriction.
• 1:28:06
  Rebecca Berens MD: Or is it, on the kind of inappropriate hunger cues related to insulin signaling issues or, other hormonal issues or whatever.
• 1:28:15
  Rebecca Berens MD: 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.
• 1:28:32
  Rebecca Berens MD: 'cause that's really not informed consent.
• 1:28:34
  Sonia Singh MD: Yeah.
• 1:28:35
  Sonia Singh MD: 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.
• 1:28:42
  Sonia Singh MD: So I feel like we should just briefly talk about that.
• 1:28:44
  Sonia Singh MD: Tell me, give me your thoughts on what you think about the ability of these meds to reduce food noise for people.
• 1:28:52
  Rebecca Berens MD: Yeah.
• 1:28:53
  Rebecca Berens MD: So I think food noise is such an interesting concept because I don't think anyone used the word food noise before 2021.
• 1:28:59
  Rebecca Berens MD: No.
• 1:28:59
  Sonia Singh MD: Yes.
• 1:29:00
  Sonia Singh MD: It's totally a new phenomenon.
• 1:29:01
  Rebecca Berens MD: And it's how does one differentiate between hunger and food noise?
• 1:29:05
  Rebecca Berens MD: Like we are supposed to have hunger.
• 1:29:08
  Rebecca Berens MD: That is a normal physiological signal.
• 1:29:10
  Rebecca Berens MD: Signal that we're supposed to have.
• 1:29:12
  Sonia Singh MD: Yes.
• 1:29:13
  Rebecca Berens MD: And.
• 1:29:14
  Rebecca Berens MD: We ha we, that is how we survive.
• 1:29:16
  Rebecca Berens MD: Like we get hungry, we eat food, we derive pleasure from eating food that makes us seek out that food.
• 1:29:21
  Rebecca Berens MD: It, that this is how we're wired, right?
• 1:29:22
  Sonia Singh MD: Yeah.
• 1:29:23
  Rebecca Berens MD: 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.
• 1:29:35
  Rebecca Berens MD: Yes.
• 1:29:36
  Rebecca Berens MD: Thinking about food, like what am I gonna be eat able to eat something there?
• 1:29:39
  Rebecca Berens MD: I can't eat this thing.
• 1:29:40
  Rebecca Berens MD: 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.
• 1:29:47
  Rebecca Berens MD: 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.
• 1:29:59
  Rebecca Berens MD: 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.
• 1:30:17
  Rebecca Berens MD: 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.
• 1:30:27
  Sonia Singh MD: Right.
• 1:30:27
  Rebecca Berens MD: And so you have to be able to tease it out.
• 1:30:29
  Rebecca Berens MD: And before these meds ever existed, this was something that was.
• 1:30:34
  Rebecca Berens MD: Talked about all the time with eating disorder specialists, with these patients of trying to reset and better understand hunger cues.
• 1:30:41
  Rebecca Berens MD: When is it true hunger?
• 1:30:42
  Rebecca Berens MD: When is it emotional hunger?
• 1:30:44
  Rebecca Berens MD: When is it eating for pleasure, just'cause it's fun?
• 1:30:47
  Rebecca Berens MD: When is it maybe an issue like this is maybe something more medically going on.
• 1:30:52
  Rebecca Berens MD: That is part of what is teased out in eating disorder treatment.
• 1:30:56
  Rebecca Berens MD: 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.
• 1:31:04
  Rebecca Berens MD: 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.
• 1:31:11
  Rebecca Berens MD: And I think a lot of this could be avoided if we did not have that preoccupation from such a young age.
• 1:31:16
  Rebecca Berens MD: 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.
• 1:31:29
  Rebecca Berens MD: And it's built up over time.
• 1:31:30
  Rebecca Berens MD: So I think turning off food noise is not universally a good thing.
• 1:31:35
  Rebecca Berens MD: And we should really understand what food noise means to that patient.
• 1:31:39
  Rebecca Berens MD: 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.
• 1:31:51
  Rebecca Berens MD: 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
• 1:31:59
  Speaker 3: yeah.
• 1:31:59
  Rebecca Berens MD: Not getting enough protein even and so you have to be very careful about that.
• 1:32:03
  Rebecca Berens MD: 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.
• 1:32:18
  Rebecca Berens MD: It is helpful to them to have support with that.
• 1:32:22
  Sonia Singh MD: Yeah, I, you're making such a good point about how heterogeneous, the idea of food noise can be.
• 1:32:27
  Sonia Singh MD: 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.
• 1:32:37
  Sonia Singh MD: And I'm just like, oh, should I eat this?
• 1:32:39
  Sonia Singh MD: Or is it better to that or should I eat this?
• 1:32:40
  Sonia Singh MD: 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.
• 1:32:44
  Sonia Singh MD: I'm just gonna have a granola bar.
• 1:32:46
  Sonia Singh MD: But that is very different than somebody who's having appropriate, hunger cues in response to restriction.
• 1:32:52
  Sonia Singh MD: It's very different than somebody who like you said, has a pre true preoccupation with food related to eating disorder.
• 1:32:57
  Sonia Singh MD: So yeah that, that's a great point.
• 1:32:59
  Sonia Singh MD: That food noise in itself is not necessarily something that needs.
• 1:33:03
  Sonia Singh MD: Pathology that needs treatment and it's can mean a lot of different things and be a lot of different things.
• 1:33:08
  Sonia Singh MD: 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.
• 1:33:19
  Sonia Singh MD: 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.
• 1:33:30
  Sonia Singh MD: I think they called it some point, right?
• 1:33:33
  Sonia Singh MD: Yeah.
• 1:33:33
  Sonia Singh MD: And over the next few decades, the ideal body type really shifted a little bit towards a fuller curvier body in a way.
• 1:33:40
  Sonia Singh MD: 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.
• 1:34:13
  Sonia Singh MD: I don't know.
• 1:34:13
  Sonia Singh MD: I'm curious about your thoughts about that.
• 1:34:15
  Sonia Singh MD: That feels to me like a big societal risk and harm that is Happening right now.
• 1:34:20
  Rebecca Berens MD: Yeah, no, it definitely is.
• 1:34:21
  Rebecca Berens MD: And I think I said at the beginning, I've seen people saying things like, now there's no excuse to be fat.
• 1:34:26
  Rebecca Berens MD: It is very stigmatizing.
• 1:34:28
  Sonia Singh MD: Yeah.
• 1:34:28
  Rebecca Berens MD: Because if someone has chosen based on the available risks and benefits not to take this medication
• 1:34:35
  Sonia Singh MD: Yeah.
• 1:34:36
  Rebecca Berens MD: And they have a larger body size now, everyone's what's wrong with you?
• 1:34:40
  Rebecca Berens MD: Which they were already saying that before.
• 1:34:41
  Rebecca Berens MD: But now it's it's like amplifying that, that negativity.
• 1:34:45
  Rebecca Berens MD: 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.
• 1:34:57
  Rebecca Berens MD: And not just to meet some sort of societal ideal.
• 1:35:02
  Rebecca Berens MD: Because it's very important that we not send that messaging.
• 1:35:06
  Rebecca Berens MD: 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.
• 1:35:18
  Rebecca Berens MD: 'Cause I, the other thing that I really believe is that, dieting is not new.
• 1:35:22
  Rebecca Berens MD: Dieting didn't start in the nineties.
• 1:35:24
  Rebecca Berens MD: Yeah.
• 1:35:24
  Rebecca Berens MD: Dining's been going on since many years ago.
• 1:35:26
  Rebecca Berens MD: I, you've probably seen the ads from the fifties, like the white wine and boiled egg diet.
• 1:35:30
  Rebecca Berens MD: Have you seen that meme on social media?
• 1:35:31
  Rebecca Berens MD: 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.
• 1:35:40
  Rebecca Berens MD: 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.
• 1:35:59
  Rebecca Berens MD: Yeah.
• 1:35:59
  Rebecca Berens MD: 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.
• 1:36:17
  Rebecca Berens MD: Yeah.
• 1:36:17
  Rebecca Berens MD: And so it, I do think that's another consideration that we have to be thinking about.
• 1:36:22
  Rebecca Berens MD: 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.
• 1:36:32
  Sonia Singh MD: Okay.
• 1:36:32
  Sonia Singh MD: So why don't we finish the episode with how we would talk to our patients about GLP ones.
• 1:36:38
  Rebecca Berens MD: 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.
• 1:36:54
  Rebecca Berens MD: What is the data actually show and what are the risks and benefits?
• 1:36:56
  Rebecca Berens MD: And then I think for, wait for everyone really we should be screening for disordered eating.
• 1:37:04
  Rebecca Berens MD: I really think we should, because I think it's so much more common than people realize.
• 1:37:08
  Rebecca Berens MD: And I don't know of any PCP that screens for it.
• 1:37:11
  Rebecca Berens MD: Did you ever get any training on screening?
• 1:37:12
  Sonia Singh MD: Never.
• 1:37:13
  Sonia Singh MD: Never?
• 1:37:13
  Rebecca Berens MD: Yeah.
• 1:37:14
  Sonia Singh MD: And what is an appropriate screening tool or like
• 1:37:16
  Rebecca Berens MD: a so there are a few one is called the Scoff.
• 1:37:19
  Rebecca Berens MD: And the scoff is like a quick five question screening tool.
• 1:37:23
  Rebecca Berens MD: That can be, it could be done in really quickly in a visit.
• 1:37:27
  Rebecca Berens MD: Just five questions.
• 1:37:28
  Rebecca Berens MD: The other one's called the ESP, which is the eating disorder screen for primary care.
• 1:37:32
  Rebecca Berens MD: And I'll link to those in in our substack.
• 1:37:35
  Rebecca Berens MD: But these are quick just a few questions, screeners that, that could be used.
• 1:37:39
  Rebecca Berens MD: And again, anytime you're screening, what are you gonna do with that screening if it's positive, right?
• 1:37:43
  Rebecca Berens MD: You always have to have a plan for your intervention after you've screened.
• 1:37:47
  Rebecca Berens MD: 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.
• 1:37:57
  Rebecca Berens MD: 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.
• 1:38:06
  Sonia Singh MD: Yeah.
• 1:38:08
  Sonia Singh MD: Yeah.
• 1:38:08
  Sonia Singh MD: I'm also curious to know like how often in PCP visits, it would be really interesting to see like a study on this.
• 1:38:13
  Sonia Singh MD: 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.
• 1:38:27
  Sonia Singh MD: There's a whole, you, I think you put it in the references.
• 1:38:29
  Sonia Singh MD: 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.
• 1:38:39
  Sonia Singh MD: So yeah, I think all of that is probably, falls under the umbrella of full informed consent and adequate counseling around these meds.
• 1:38:46
  Rebecca Berens MD: And I really feel, we've talked about dieticians many times.
• 1:38:49
  Rebecca Berens MD: 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.
• 1:39:03
  Rebecca Berens MD: About about that.
• 1:39:04
  Rebecca Berens MD: And I, I.
• 1:39:07
  Rebecca Berens MD: Strongly recommend that all of my patients that are taking a GLP one are seeing a dietician.
• 1:39:10
  Rebecca Berens MD: 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.
• 1:39:23
  Rebecca Berens MD: So I, I strongly encourage that and I always refer patients to see a dietician if they're starting,
• 1:39:27
  Sonia Singh MD: 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.
• 1:39:36
  Sonia Singh MD: Of having a hard time finding somebody to see my patients or like that they were getting it covered.
• 1:39:42
  Rebecca Berens MD: So I have not really had a hard time, I gotta be honest.
• 1:39:46
  Rebecca Berens MD: 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.
• 1:40:00
  Rebecca Berens MD: They have licenses.
• 1:40:01
  Rebecca Berens MD: Yeah.
• 1:40:01
  Rebecca Berens MD: Where you can go and select for like specific conditions that you have.
• 1:40:05
  Rebecca Berens MD: We can maybe link some of these in the substack.
• 1:40:08
  Rebecca Berens MD: But, if you're starting someone on a GLP one, theoretically there is a metabolic issue that you're concerned about.
• 1:40:14
  Sonia Singh MD: Yeah.
• 1:40:15
  Rebecca Berens MD: Right.
• 1:40:16
  Sonia Singh MD: Yeah,
• 1:40:16
  Rebecca Berens MD: that's
• 1:40:16
  Sonia Singh MD: true.
• 1:40:16
  Sonia Singh MD: Yeah.
• 1:40:16
  Rebecca Berens MD: Theoretically they have high blood pressure or pre-diabetes or hyperlipidemia or there should be a diagnosis.
• 1:40:22
  Rebecca Berens MD: 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?
• 1:40:28
  Sonia Singh MD: 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.
• 1:40:34
  Sonia Singh MD: So like those patients, oftentimes it is not easy to get, I don't know.
• 1:40:39
  Sonia Singh MD: I haven't been in insurance-based care now for five years.
• 1:40:41
  Sonia Singh MD: Yeah.
• 1:40:41
  Sonia Singh MD: So maybe it has gotten easier.
• 1:40:42
  Sonia Singh MD: I
• 1:40:42
  Rebecca Berens MD: mean I think either they have a metabolic condition that you can diagnose or they don't.
• 1:40:49
  Rebecca Berens MD: And if they don't, I would ask, I would just ask yourself the question, what is the benefit here for this patient?
• 1:40:54
  Rebecca Berens MD: And and also you can also pay cash to see a dietician.
• 1:40:58
  Rebecca Berens MD: And I think that's the other thing that I think a lot of our insurance-based colleagues forget about.
• 1:41:02
  Rebecca Berens MD: 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.
• 1:41:19
  Rebecca Berens MD: Yeah.
• 1:41:19
  Rebecca Berens MD: And they will probably pay for it.
• 1:41:20
  Rebecca Berens MD: Yeah.
• 1:41:21
  Rebecca Berens MD: 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.
• 1:41:32
  Rebecca Berens MD: It's up to them, but I think it's good to recommend it.
• 1:41:36
  Sonia Singh MD: Yeah, totally agree.
• 1:41:37
  Sonia Singh MD: And I've used there's one we're probably thinking of the same one.
• 1:41:40
  Sonia Singh MD: There's one like big online telehealth platform that has our actual rds and they do take a lot of insurances.
• 1:41:47
  Sonia Singh MD: And so I've, I have had success with that one.
• 1:41:49
  Sonia Singh MD: We'll link we're not affiliated with them in any way, but We'll, we will link them in the substack.
• 1:41:54
  Sonia Singh MD: Yeah.
• 1:41:55
  Rebecca Berens MD: Yeah.
• 1:41:55
  Rebecca Berens MD: And we do have great options locally too.
• 1:41:57
  Rebecca Berens MD: Like we really do.
• 1:41:58
  Rebecca Berens MD: Yeah.
• 1:41:58
  Rebecca Berens MD: 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.
• 1:42:06
  Rebecca Berens MD: I've realized.
• 1:42:07
  Rebecca Berens MD: I think because the systems don't prioritize them very much.
• 1:42:11
  Rebecca Berens MD: Yeah.
• 1:42:11
  Rebecca Berens MD: And so they're siloed away.
• 1:42:13
  Rebecca Berens MD: But there's a lot of dieticians out there in private practice who can help your patients.
• 1:42:17
  Sonia Singh MD: 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.
• 1:42:29
  Sonia Singh MD: But I think just the logistics of it make it sometimes challenging for people, but okay.
• 1:42:34
  Sonia Singh MD: And then so we talked about honesty, about the risks and benefits.
• 1:42:38
  Sonia Singh MD: We talked about careful monitoring for side effects and perhaps using the minimum dose necessary.
• 1:42:46
  Sonia Singh MD: 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.
• 1:42:59
  Sonia Singh MD: You're gonna be fine.
• 1:43:00
  Sonia Singh MD: There's no side don't worry about anything.
• 1:43:01
  Sonia Singh MD: No monitoring required.
• 1:43:02
  Sonia Singh MD: 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.
• 1:43:15
  Sonia Singh MD: You still, need a well-trained medical professional prescribing and monitoring these ideally.
• 1:43:21
  Rebecca Berens MD: Yeah.
• 1:43:21
  Rebecca Berens MD: And I think that monitoring part is so key.
• 1:43:23
  Rebecca Berens MD: And, I think, again the, for the minimum dose necessary, like we, there's no rush to this.
• 1:43:28
  Rebecca Berens MD: I also see people like really rushing to taper them up to the highest dose.
• 1:43:32
  Rebecca Berens MD: And I'm just like for why?
• 1:43:34
  Rebecca Berens MD: For why.
• 1:43:35
  Rebecca Berens MD: Because it, to me, that just makes it less sustainable.
• 1:43:38
  Rebecca Berens MD: And we can reduce GI side effects.
• 1:43:40
  Rebecca Berens MD: 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.
• 1:43:49
  Rebecca Berens MD: 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.
• 1:43:56
  Rebecca Berens MD: Yeah.
• 1:43:57
  Rebecca Berens MD: And people and they don't restrict people from adjusting their doses.
• 1:44:03
  Rebecca Berens MD: 'Cause now that's a big issue.
• 1:44:04
  Rebecca Berens MD: If people could theoretically buy a vial that is a larger dose and then split it up into smaller doses.
• 1:44:09
  Rebecca Berens MD: Yeah.
• 1:44:09
  Rebecca Berens MD: And it would be more cost effective.
• 1:44:11
  Rebecca Berens MD: But of course they don't want them to do that.
• 1:44:13
  Rebecca Berens MD: 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.
• 1:44:24
  Rebecca Berens MD: And I hope that in the future we'll move towards that.
• 1:44:26
  Sonia Singh MD: Yeah.
• 1:44:28
  Sonia Singh MD: Okay.
• 1:44:28
  Sonia Singh MD: Where can people go for more info?
• 1:44:31
  Rebecca Berens MD: So I'm gonna link all of the articles that we talked about today in our substack.
• 1:44:35
  Rebecca Berens MD: And there in particular, there's a great informed consent resource from the medical students for size inclusivity.
• 1:44:42
  Rebecca Berens MD: It is from 2023, so it's a little bit out of date now.
• 1:44:44
  Rebecca Berens MD: 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.
• 1:44:52
  Rebecca Berens MD: And I think it's a good starting point for people.
• 1:44:54
  Sonia Singh MD: Oh, this is so cool.
• 1:44:55
  Sonia Singh MD: Yeah, it's like a 10 page PDF with a lot of good information.
• 1:44:58
  Sonia Singh MD: So that's an awesome resource.
• 1:45:00
  Sonia Singh MD: Thank you for sharing that.
• 1:45:02
  Sonia Singh MD: Okay.
• 1:45:03
  Sonia Singh MD: All right, that brings us to the end of the episode.
• 1:45:05
  Sonia Singh MD: Thanks Rebecca.
• 1:45:06
  Rebecca Berens MD: Thanks Sonia.
• 1:45:11
  Sonia Singh MD: Hey guys.
• 1:45:12
  Sonia Singh MD: Last but not least, we have a very important disclaimer.
• 1:45:15
  Sonia Singh MD: This podcast is intended for educational and entertainment purposes only.
• 1:45:19
  Sonia Singh MD: The content shared on this podcast, including but not limited to opinions, research discussions, case examples, and commentary, is not medical advice and should not be considered a substitute for professional medical evaluation, diagnosis, or treatment.
• 1:45:34
  Sonia Singh MD: Listening to this podcast does not establish a physician-patient relationship between you and the hosts.
• 1:45:39
  Sonia Singh MD: We are doctors, but not your doctors.
• 1:45:42
  Sonia Singh MD: Any medical topics discussed are presented for general informational purposes and may not apply to your individual circumstances.
• 1:45:49
  Sonia Singh MD: Always seek the advice of your own qualified healthcare professional regarding any questions you have about your health.
• 1:45:54
  Sonia Singh MD: Medical conditions or treatment options, never disregard or delay medical advice because of something you've heard on this podcast.
• 1:46:01
  Sonia Singh MD: While the hosts are licensed physicians, the views and opinions expressed are our own and do not represent those of our employers, institutions, organizations, or professional societies with which we are affiliated, although we do our best to stay up to date.
• 1:46:15
  Sonia Singh MD: Please note that this podcast includes discussion of emerging research, evolving medical concepts, and differing professional opinions.
• 1:46:22
  Sonia Singh MD: Medicine is not static and information may change over time.
• 1:46:26
  Sonia Singh MD: We, the hosts make no guarantees about the accuracy, completeness, or applicability of this content, and we disclaim any liability for actions taken or not taken based on the information provided in this podcast by listening to the Antisocial Doctors Podcast, you have agreed to these terms.
• 1:46:42
  Sonia Singh MD: Thanks again for joining us.