Latest / Wellness, Actually with Emily Oster & Perry Wilson, MD / Ozempic 101: A doctor explains the data and science behind weight-loss drugs

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Ozempic 101: A doctor explains the data and science behind weight-loss drugs · Wellness, Actually with Emily Oster & Perry Wilson, MD

• 0:01
  Speaker 1: This is parent data. I'm Emily Ostro. If you listen
• 0:10
  Speaker 1: to the news, you hear a lot about ozembic.
• 0:16
  Speaker 2: Miles of a trizone.
• 0:19
  Speaker 1: It's actually been around for a couple of decades, but
• 0:21
  Speaker 1: only in the last couple of years.
• 0:22
  Speaker 3: It feels like it's everywhere all the time. Weight loss
• 0:25
  Speaker 3: treatment is going through a revolution.
• 0:27
  Speaker 2: Diabetes drugs are in hot demand over the dramatic weight
• 0:29
  Speaker 2: loss effects. You so celebrities doing it latest crazy in Hollywood,
• 0:33
  Speaker 2: but it's spready to beyond Hollywood. But the results of
• 0:35
  Speaker 2: Peter almost too good to be true.
• 0:39
  Speaker 1: We often use ozembic as a shorthand for a broader
• 0:42
  Speaker 1: class of GLP one drugs. They're also called samaglatides, but
• 0:46
  Speaker 1: you may have heard of Govi, Manjaro, Rebelsis, zepp Bound. Broadly,
• 0:52
  Speaker 1: these all do roughly the same thing, which is that
• 0:54
  Speaker 1: they treat type two diabetes and they help people lose weight.
• 1:02
  Speaker 1: So much of the discussion in popular culture about this
• 1:06
  Speaker 1: is about these big picture social questions around these drugs.
• 1:11
  Speaker 3: What are the societal.
• 1:12
  Speaker 1: Implications of all of these drugs becoming available and helping
• 1:17
  Speaker 1: so many people lose so much weight? How does this
• 1:19
  Speaker 1: change our relationship to the food system. How does this
• 1:23
  Speaker 1: change the stock market price for Nabisco? How should we
• 1:27
  Speaker 1: think about body positivity and the way we think about
• 1:31
  Speaker 1: weight and how that relates to these new options for
• 1:34
  Speaker 1: weight loss.
• 1:36
  Speaker 3: But today I.
• 1:38
  Speaker 1: Wanted to talk about a narrower question and one I
• 1:41
  Speaker 1: think many people ask, which is are these drugs right
• 1:45
  Speaker 1: for me? And so I invited an endochronologist to address
• 1:49
  Speaker 1: this smaller picture. You may remember doctor Gillian Goddard from
• 1:54
  Speaker 1: the episode on perimenopause and birth control Later in life.
• 1:58
  Speaker 1: She writes our newsletter Hot Flash, which you should be
• 2:01
  Speaker 1: subscribed to immediately.
• 2:03
  Speaker 3: I love it. And today she and I are going
• 2:06
  Speaker 3: to talk about GLP one drugs.
• 2:08
  Speaker 1: We're going to talk about how she prescribes them as
• 2:11
  Speaker 1: an endocrinologist, about who is a good candidate for these,
• 2:16
  Speaker 1: and about how the findings from trials do and do
• 2:20
  Speaker 1: not translate into the way she uses these drugs in
• 2:23
  Speaker 1: her patients. I was interested to ask her, how do
• 2:27
  Speaker 1: you get people on the drugs? What kind of side
• 2:30
  Speaker 1: effects of the experience do they come off the drugs?
• 2:33
  Speaker 1: Do you find that people have to take these forever?
• 2:37
  Speaker 1: I'm hoping that this conversation will be the path to
• 2:41
  Speaker 1: a conversation that you could have with your doctor if
• 2:44
  Speaker 1: this is something that feels right for you, if you're
• 2:47
  Speaker 1: curious about the drugs yourself, or just generally interested in
• 2:51
  Speaker 1: what feels like an inescapable phenomenon. This is the episode
• 2:55
  Speaker 1: for everything you want to know about ozepic but have
• 2:58
  Speaker 1: no one to ask it to. And before we get going,
• 3:01
  Speaker 1: I want to be clear. These drugs are not for everyone.
• 3:05
  Speaker 1: Plenty of people have no interest in them at all,
• 3:08
  Speaker 1: and I am certainly not here and we're certainly not
• 3:11
  Speaker 1: here to talk anyone into anything. But the drugs are here,
• 3:15
  Speaker 1: probably to stay, and I think it is important to
• 3:17
  Speaker 1: understand how they work after the break our own doctor
• 3:22
  Speaker 1: Jillian Goddard. Doctor Jillian Goddard, thank you for coming back
• 3:33
  Speaker 1: to parent Data.
• 3:34
  Speaker 2: I'm so excited to be back.
• 3:36
  Speaker 1: So you write for parent Data, you write our newsletter
• 3:40
  Speaker 1: called the Hot Flash, and you're an endocrinologist.
• 3:44
  Speaker 3: Can you tell us what that is? Sure?
• 3:47
  Speaker 2: So, I'm an adult under chronologist, which means that I
• 3:53
  Speaker 2: take care of people who are having problems with their
• 3:57
  Speaker 2: hormones and the glands that make those hormone. So in
• 4:02
  Speaker 2: my typical patients will have problems like thyroid problems or
• 4:08
  Speaker 2: reproductive problems or diabetes. Those are the most common things
• 4:12
  Speaker 2: that I see in my practice.
• 4:14
  Speaker 3: And how would I know that I need to see
• 4:15
  Speaker 3: an unocrinologist?
• 4:18
  Speaker 2: You know, it's really sometimes it's really challenging to know
• 4:21
  Speaker 2: when you need to see an endochronologist. And there's not
• 4:24
  Speaker 2: very many of us. There's less than nine thousand practicing
• 4:27
  Speaker 2: endochronologists in the United States, and so sometimes even if
• 4:31
  Speaker 2: you need to see an endochronologist, it's not the easiest
• 4:34
  Speaker 2: thing to accomplish. But I think that the things that
• 4:38
  Speaker 2: tend to send people to see me are things like
• 4:42
  Speaker 2: not having regular periods and they're gynecologists has done some
• 4:45
  Speaker 2: work up and they can't seem to figure out why,
• 4:50
  Speaker 2: or having problems with blood sugar, or I see a
• 4:53
  Speaker 2: lot of people who are struggling with their weight and
• 4:58
  Speaker 2: it's having impacts on their health.
• 5:01
  Speaker 1: So that last pieces we're going to talk about today,
• 5:03
  Speaker 1: I want to have a conversation about semiglu kaids, ozempic
• 5:08
  Speaker 1: zep bound, majaro, wigovi, whatever is the name of the
• 5:12
  Speaker 1: thing you're hearing about. And I think this is an
• 5:15
  Speaker 1: important conversation because we hear.
• 5:18
  Speaker 3: About these all the time.
• 5:19
  Speaker 1: So if I had to categorize the New York Times
• 5:22
  Speaker 1: well section of late, it's just literally a list of
• 5:26
  Speaker 1: articles about ozempic and like every third one. Then they'll
• 5:30
  Speaker 1: they'll be like, oh, also, like should you drink raw milk?
• 5:33
  Speaker 3: And then we're just like back to ozempic. Don't drink
• 5:36
  Speaker 3: raw milk.
• 5:37
  Speaker 1: So many of those articles are either about a new
• 5:41
  Speaker 1: study which says ozembic also fixes this problem that a
• 5:45
  Speaker 1: lot of people have, or it is a kind of
• 5:49
  Speaker 1: big picture question about, you know, how society is going
• 5:54
  Speaker 1: to change with the result of ozepic. And some of
• 5:57
  Speaker 1: these are quite interesting as an economist, So people were
• 6:00
  Speaker 1: talking about are we headed for a collapse of the
• 6:03
  Speaker 1: snack food market? And you know, should you short doritos
• 6:07
  Speaker 1: in the stock market or go long you know, peloton
• 6:11
  Speaker 1: or whatever it is your peloton.
• 6:12
  Speaker 3: I don't know. Economics is complicated.
• 6:15
  Speaker 1: But the conversation I want to have today is about
• 6:18
  Speaker 1: being a doctor treating ozembic on a much lower level,
• 6:22
  Speaker 1: because that's something that you do a lot.
• 6:26
  Speaker 3: Correct I do it a lot all day every day.
• 6:31
  Speaker 1: So let's start with the most basic question in case
• 6:34
  Speaker 1: people are not reading every third article in the New
• 6:36
  Speaker 1: York Times Fall section. Tell me about these drugs and
• 6:40
  Speaker 1: why there is so much discussion of them.
• 6:43
  Speaker 2: Sure, so, most of these drugs are in a class
• 6:49
  Speaker 2: called GLP one agonis. GLP one is a hormone that
• 6:54
  Speaker 2: we all have in our bodies, and it impacts how
• 6:58
  Speaker 2: our bodies produce insulin, how our bodies respond to insulin,
• 7:03
  Speaker 2: and how we metabolize sugar. They're not new drugs. The
• 7:07
  Speaker 2: first GLP one was approved by the FDA in two
• 7:11
  Speaker 2: thousand and four and they were originally developed to treat
• 7:15
  Speaker 2: type two diabetes and they're very effective treatments for type
• 7:19
  Speaker 2: two diabetes. Over the last twenty years, as is likely
• 7:24
  Speaker 2: to happen in a big market, the class has gotten
• 7:28
  Speaker 2: very crowded. There are many many glp ones and we've
• 7:34
  Speaker 2: started exploring other uses for them. So smaglatide, which is
• 7:40
  Speaker 2: ozeenbic and wigov is actually not the first GLP one
• 7:44
  Speaker 2: that was approved for use for weight loss. The first
• 7:48
  Speaker 2: GLP one that was approved for use for weight loss
• 7:50
  Speaker 2: was loraglatide and it was approved in twenty fourteen. So
• 7:54
  Speaker 2: this idea is not new at all, and in fact,
• 7:58
  Speaker 2: under chronologists have been used GLP one agonists off label
• 8:02
  Speaker 2: to help people lose weight since they were approved in
• 8:06
  Speaker 2: two thousand and four. What's different is how effective these
• 8:12
  Speaker 2: medicines are and how frequently they have to be given.
• 8:16
  Speaker 2: So the very first GLP one exenotide was a twice
• 8:22
  Speaker 2: daily injection and that was difficult to get even type
• 8:25
  Speaker 2: two diabetics to do. Smaglatide and terzepetide, So samaglatide again
• 8:32
  Speaker 2: is ozebic and wigov terzepetide is moonjyro and zep bound.
• 8:37
  Speaker 2: Those medicines are once weekly medicines.
• 8:40
  Speaker 3: But it's still an injection.
• 8:42
  Speaker 2: There's still an injection. There's one oral GLP one agonist,
• 8:46
  Speaker 2: it's semaglatide and the brand name is Rabelsis, and it's
• 8:50
  Speaker 2: not approved for weight loss. It's only approved for treating
• 8:53
  Speaker 2: type two diabetes.
• 8:54
  Speaker 1: So far is there a let's I want to talk
• 8:57
  Speaker 1: a little bit about this, this sort of dose and treatment,
• 9:01
  Speaker 1: just to people understand that the landscape. Obviously people would
• 9:06
  Speaker 1: prefer to take this in a pill. Why are we
• 9:08
  Speaker 1: not all taking it in a pill?
• 9:11
  Speaker 2: So only about one percent of the drug is absorbed
• 9:15
  Speaker 2: if you just so, if you just orally took some maglatide,
• 9:19
  Speaker 2: only about one percent of what you put in your
• 9:22
  Speaker 2: mouth would be absorbed through your gastrointestinal system, so super inefficient.
• 9:27
  Speaker 2: It took them, you know, the better part of the
• 9:30
  Speaker 2: fifty first fifteen years these drugs are on the market.
• 9:33
  Speaker 2: To come up with a pill, the pill that is available,
• 9:37
  Speaker 2: which is which is rybelsis, you have to take that
• 9:40
  Speaker 2: pill first thing in the morning on an empty stomach,
• 9:44
  Speaker 2: with not more than half a cup of water. You
• 9:47
  Speaker 2: have to wait thirty minutes and then you can have
• 9:51
  Speaker 2: something to eat or drink at that point. And so
• 9:53
  Speaker 2: there's lots of room for user error. But it's conceivable
• 9:58
  Speaker 2: that Ribelsa's in large enough doses to impact wheat or
• 10:03
  Speaker 2: some other form of these medicines that oral will come
• 10:07
  Speaker 2: out in the future. I would just say at this point,
• 10:11
  Speaker 2: we can't get enough of these drugs into you through
• 10:15
  Speaker 2: a pill to have them be particularly effective for weight loss.
• 10:19
  Speaker 1: And so people have injections. You can do the injection
• 10:22
  Speaker 1: yourself at home.
• 10:23
  Speaker 2: It's super easy. Most of the products that are specifically
• 10:28
  Speaker 2: for treating obesity are in single use autoinjectors. They look
• 10:34
  Speaker 2: a lot like an EpiPen.
• 10:36
  Speaker 3: Okay, So.
• 10:39
  Speaker 1: There have been other weight loss drugs in the past,
• 10:44
  Speaker 1: with some of which have turned out to be terrible
• 10:47
  Speaker 1: for you, but most of which.
• 10:48
  Speaker 3: Have turned out not to work.
• 10:50
  Speaker 1: So, in a sense, the big delta here feels to
• 10:54
  Speaker 1: me like when you talk to people about being on
• 10:59
  Speaker 1: one of these medications for weight loss, they will talk
• 11:01
  Speaker 1: about it as a very big sea change in how
• 11:06
  Speaker 1: they are experiencing food and fullness, which feels very different
• 11:12
  Speaker 1: than the way people would talk about some of the
• 11:14
  Speaker 1: older kinds of medications. So, first of all, is that
• 11:18
  Speaker 1: consistent with your experience? And if yes, do we have
• 11:21
  Speaker 1: a sense of why this is so different?
• 11:24
  Speaker 2: Yeah, so I would say that's definitely consistent with my experience.
• 11:30
  Speaker 2: When I first started in my practice, the options were
• 11:34
  Speaker 2: really some old fashioned amphetamine based pills that suppressed your
• 11:39
  Speaker 2: appetite and made you feel little jittery.
• 11:43
  Speaker 1: Mother's little helper, I think, is what those were called
• 11:45
  Speaker 1: in the nineteen fifties.
• 11:46
  Speaker 3: Literally, it's right.
• 11:47
  Speaker 2: That's right, that's right, And they have they've been around since, yes,
• 11:54
  Speaker 2: but they you know, they had a lot of side effects.
• 11:56
  Speaker 2: They people couldn't sleep after they took them. They also
• 12:00
  Speaker 2: didn't work for very long. So they're still around and
• 12:04
  Speaker 2: you can give them to people and they will suppress
• 12:07
  Speaker 2: people's appetite, and they will make them feel a little zingy,
• 12:12
  Speaker 2: but they will not they don't work for very long.
• 12:15
  Speaker 2: After two months, people's appetite starts to come back, they
• 12:18
  Speaker 2: start to regain the weight that they've lost, and most
• 12:21
  Speaker 2: of us need more than a two month jump start
• 12:24
  Speaker 2: if we're really going to have any impact on to
• 12:27
  Speaker 2: get significant weight loss. There have been some other weight
• 12:32
  Speaker 2: loss medicines over the years that worked in different ways.
• 12:36
  Speaker 2: We used the approprion, which is also well butrin for
• 12:41
  Speaker 2: a weight loss, which sometimes would help people with cravings,
• 12:45
  Speaker 2: but there really hasn't been anything that's as effective as
• 12:49
  Speaker 2: this class of medications. Is. The kind of weight loss
• 12:53
  Speaker 2: we see with this class of medicines is more akin
• 12:56
  Speaker 2: to the kind of weight loss people see with bariatric
• 12:59
  Speaker 2: surgery than it is to the kind of weight loss
• 13:01
  Speaker 2: that people saw in the past with older a weight
• 13:04
  Speaker 2: loss medication. So they really are paradigm shifting. Why. There's
• 13:11
  Speaker 2: a lot of reasons why. For one thing, we're really
• 13:15
  Speaker 2: starting to understand that a lot of what gets in
• 13:18
  Speaker 2: people's way as far as losing weight is not appetite.
• 13:22
  Speaker 2: It's not appetite and it's not what they're eating. It's
• 13:25
  Speaker 2: how their body is processing what they're eating. If somebody's
• 13:30
  Speaker 2: not processing carbohydrates well and that's impacting how they're storing carbohydrates,
• 13:39
  Speaker 2: and we can change how they're processing carbohydrates so that
• 13:42
  Speaker 2: they're processing them more typically, then all of a sudden
• 13:47
  Speaker 2: we can have a big impact. The other thing that
• 13:50
  Speaker 2: we're really starting to understand is that GLP one, the hormone,
• 13:55
  Speaker 2: and insulin actually have effects in the brain around tiety,
• 14:01
  Speaker 2: around the rewards system, and around metabolic rate, and all
• 14:07
  Speaker 2: these things are really closely linked. And so when you
• 14:10
  Speaker 2: give someone GLP one, you raise their GLP one levels
• 14:14
  Speaker 2: in their brain and you decrease the insulin levels in
• 14:17
  Speaker 2: their brain, and that will have big impacts on things
• 14:21
  Speaker 2: like food noise and the reward people feel from consuming,
• 14:28
  Speaker 2: you know, something super salty and crunchy or sugary.
• 14:33
  Speaker 1: So let's turn to the prescribing behavior here, because i'd
• 14:37
  Speaker 1: love to talk about your experience using this with your patients.
• 14:41
  Speaker 1: So how do you evaluate whether someone is a good candidate.
• 14:47
  Speaker 1: Someone comes in to see you, they say, I heard
• 14:49
  Speaker 1: about this drug, I want it. How do you think
• 14:52
  Speaker 1: about whether that's a good idea.
• 14:56
  Speaker 2: There's a few things that I take into consideration. When
• 14:59
  Speaker 2: I think about this, my first thing that I think
• 15:02
  Speaker 2: about is what have they tried to lose weight in
• 15:05
  Speaker 2: the past, and how successful have they been with those methods.
• 15:10
  Speaker 2: I will tell you usually by the time someone comes
• 15:13
  Speaker 2: to see me, they have tried everything. They've been on
• 15:18
  Speaker 2: every diet, they have done extreme dieting, they've done keto,
• 15:25
  Speaker 2: they've done literally you name it, they've done it. They've
• 15:29
  Speaker 2: tried every type of exercise. They may have tried other
• 15:32
  Speaker 2: medications in the past, and they may have had short
• 15:36
  Speaker 2: term success with those things, but they've never been able
• 15:38
  Speaker 2: to maintain the loss that they that they achieved. I've
• 15:43
  Speaker 2: had many patients come in who've already had bariatric surgery too,
• 15:47
  Speaker 2: and have regained the weight that they lost with bariatric surgery.
• 15:50
  Speaker 2: So these are not people who have just decided on
• 15:52
  Speaker 2: a whim that they need to lose ten pounds because
• 15:57
  Speaker 2: they're feeling a little uncomfortable. These are often people who've
• 16:00
  Speaker 2: had lifelong struggles with weight and they've literally tried everything.
• 16:09
  Speaker 1: Do you think about a BMI cut off? Is there
• 16:12
  Speaker 1: like an amount of weight that people would need to
• 16:14
  Speaker 1: lose that would influence whether you'd think someone was a
• 16:17
  Speaker 1: good candidate.
• 16:21
  Speaker 2: That's a tricky question because I hate BMI as a
• 16:25
  Speaker 2: measure to apply to.
• 16:26
  Speaker 3: A way I used amount of weight.
• 16:28
  Speaker 1: I changed what I was saying, But I agree BMI
• 16:30
  Speaker 1: is a problematic metric.
• 16:32
  Speaker 2: BMI is an incredibly problematic metric, but we do have
• 16:35
  Speaker 2: to take it into account because it is the metric
• 16:38
  Speaker 2: that the insurance company uses to decide whether or not
• 16:40
  Speaker 2: they're going to cover the medication. And these medications are expensive.
• 16:45
  Speaker 2: So while I don't necessarily have a BMI cut off
• 16:48
  Speaker 2: that I am looking at, and I don't use BMI
• 16:51
  Speaker 2: as a way to set a weight loss goal for
• 16:55
  Speaker 2: a patient, we do kind of have to at least
• 16:58
  Speaker 2: look at the BMI and know what it is when
• 17:01
  Speaker 2: we're thinking about getting coverage for the patient for these medications.
• 17:06
  Speaker 2: I look much more holistically at a patient who's coming
• 17:11
  Speaker 2: in to see me. I want to know what their
• 17:14
  Speaker 2: blood sugar levels look like, what their insulin levels look like.
• 17:17
  Speaker 2: Are they having blood pressure problems? Are on day on
• 17:20
  Speaker 2: cholesterol medication? Are they having problems with mobility because of weight?
• 17:28
  Speaker 2: I really care much more about how weight is impacting
• 17:34
  Speaker 2: someone's broader health when I think about these medications because
• 17:39
  Speaker 2: there's data that shows that just having a high BMI
• 17:43
  Speaker 2: in and of itself is not the problem. The problem
• 17:46
  Speaker 2: is when the weight is associated with other medical problems,
• 17:52
  Speaker 2: and that's sort of where I like to focus my
• 17:56
  Speaker 2: efforts and goals too.
• 17:59
  Speaker 1: Do you have people who come in who just say,
• 18:02
  Speaker 1: you know, I'd really like to lose this extra fifteen
• 18:05
  Speaker 1: pounds so I can fit into this dress from my
• 18:09
  Speaker 1: high school years, or like for I mean, for very
• 18:11
  Speaker 1: legitimate reasons, like which is many of us maybe would
• 18:16
  Speaker 1: like to lose an extra ten pounds.
• 18:18
  Speaker 3: I assume you see patients with that request.
• 18:21
  Speaker 2: To My office is on the Upper East side of Manhattan.
• 18:28
  Speaker 1: What do you say, because I mean, I think I
• 18:30
  Speaker 1: didn't quite put myself in this category, but I can
• 18:32
  Speaker 1: certainly see personally the instinct to be like, boy, maybe
• 18:35
  Speaker 1: i'd run faster if I was a little you know, like,
• 18:37
  Speaker 1: I can see the instinct, and so I'm curious how
• 18:40
  Speaker 1: you counsel in that situation because it sounds like your
• 18:42
  Speaker 1: answer would be no, but there must be something beyond no.
• 18:46
  Speaker 2: Yeah, I mean, I would never just tell a patient no,
• 18:49
  Speaker 2: because I don't think that's a very effective way to communicate.
• 18:54
  Speaker 2: Sort of what my concerns are, which would be, you know,
• 18:58
  Speaker 2: these medicines are not a quick fix. I tell patients
• 19:01
  Speaker 2: to expect to be on them for a minimum of
• 19:04
  Speaker 2: a year, and they're changing other things about how your
• 19:07
  Speaker 2: body is functioning and working that I think, you know,
• 19:11
  Speaker 2: you might not want to change and might have some
• 19:14
  Speaker 2: unintended consequences if you're really just looking to lose ten
• 19:18
  Speaker 2: or fifteen pounds. I also always really caution people you
• 19:22
  Speaker 2: mentioned athletic performance, always really caution people who part of
• 19:27
  Speaker 2: their goal is to improve athletic performance, because that's actually
• 19:32
  Speaker 2: a real challenge with these medications on the way these
• 19:36
  Speaker 2: medications impact appetite and metabolism can actually, in some cases
• 19:41
  Speaker 2: adversely affect people's athletic performance. So anytime I have someone
• 19:46
  Speaker 2: come in who's both whether they're you know, more professional
• 19:51
  Speaker 2: about it or an amateur who really cares about their
• 19:54
  Speaker 2: athletic performance, I always talk very carefully with them about
• 19:58
  Speaker 2: the pros and cons of these medicines, as it can
• 20:00
  Speaker 2: actually backfire, it can really adversely affect performance.
• 20:04
  Speaker 3: It's good to know.
• 20:07
  Speaker 1: So someone comes in you decide that, for various reasons,
• 20:11
  Speaker 1: looking holistically, you're going to start on these on these medications.
• 20:16
  Speaker 1: In the trials for these drugs, the way that trials
• 20:20
  Speaker 1: work is you just dose one dose.
• 20:23
  Speaker 3: So you have a trial of a dose. You know,
• 20:25
  Speaker 3: there's the dose of this.
• 20:27
  Speaker 1: Everyone gets that, and that's the dose. Because when you
• 20:31
  Speaker 1: are trying to show scientific evidence that something works, you
• 20:36
  Speaker 1: can't be messing about with how much people are getting.
• 20:39
  Speaker 1: To optimize for each individual, you need to be able
• 20:42
  Speaker 1: to show we gave everybody you know, this number of
• 20:44
  Speaker 1: milligrams this frequently, and then in the end the result
• 20:47
  Speaker 1: was this.
• 20:47
  Speaker 3: That's how you get your FDA approval, But in.
• 20:50
  Speaker 1: Your office, I that's not often how medicine works. So
• 20:55
  Speaker 1: I assume you do not start everybody on the exactly
• 20:59
  Speaker 1: the that was in the trial. So I'm curious how
• 21:02
  Speaker 1: you navigate that beginning of this process with someone and
• 21:06
  Speaker 1: why you would not maybe you can articulate better than
• 21:09
  Speaker 1: I can, why you would not just go in with
• 21:11
  Speaker 1: the trial dosage and that's what it is.
• 21:13
  Speaker 2: So that is actually a really tricky thing with these medicines.
• 21:17
  Speaker 2: So with WI GOVI specifically, they had a very strict
• 21:21
  Speaker 2: titration in the trial that involved going up on the
• 21:29
  Speaker 2: medication every single month until they were on the target
• 21:32
  Speaker 2: dose and if patients couldn't tolerate that, they had to
• 21:36
  Speaker 2: drop out of the trial. And that trial actually had
• 21:38
  Speaker 2: a very high rate of patients dropping out for side
• 21:41
  Speaker 2: effects from the medication, about fifteen percent. So I try
• 21:46
  Speaker 2: not to dose the medications in that way. We always
• 21:49
  Speaker 2: start with the lowest dose. With these medications, there's a
• 21:53
  Speaker 2: starting dose with all of them, and then my goal
• 21:57
  Speaker 2: is actually to titrate to a rate of weight loss
• 22:00
  Speaker 2: of about one to two pounds per week on average.
• 22:05
  Speaker 2: So I know when you read in the media about
• 22:07
  Speaker 2: patients or about people taking these medicines, they will say
• 22:11
  Speaker 2: I lost twenty pounds in the first month. That is
• 22:14
  Speaker 2: not my goal for people. My goal is one to
• 22:18
  Speaker 2: two pounds a week on average, and I have them
• 22:21
  Speaker 2: stay on a dose that gets them a rate of
• 22:24
  Speaker 2: weight loss in that range until it stops working. And
• 22:27
  Speaker 2: so many of my patients will stay on much lower doses.
• 22:31
  Speaker 2: And my goal with that is twofold one is I
• 22:34
  Speaker 2: think that's a much more sustainable rate of loss. I
• 22:38
  Speaker 2: think it's easier to minimize muscle loss when people are
• 22:42
  Speaker 2: not losing weight so rapidly. It also minimizes side effects.
• 22:47
  Speaker 2: So the other thing you will hear a lot about
• 22:49
  Speaker 2: with these medications, is people saying that they are throwing
• 22:55
  Speaker 2: up all the time, they're super super sick. I always
• 22:58
  Speaker 2: tell my patients you should never be throwing up. You
• 23:01
  Speaker 2: may be nauseated at times, especially within the first forty
• 23:04
  Speaker 2: eight hours of taking and taking the dose, but you
• 23:07
  Speaker 2: should never be throwing up. And if you're throwing up,
• 23:10
  Speaker 2: I want you to call me and let me know,
• 23:11
  Speaker 2: because that means we need to make a change, and
• 23:14
  Speaker 2: so a more gentle upward titration can allow us to
• 23:21
  Speaker 2: balance the benefit with some of the side effects of
• 23:25
  Speaker 2: these medications.
• 23:27
  Speaker 1: Do you find people are happy with the one to
• 23:29
  Speaker 1: two I mean, if I come in with the expectation
• 23:31
  Speaker 1: I'm gonna lose twenty pounds in the first month, and
• 23:33
  Speaker 1: then you tell me, like your expectation should be that
• 23:36
  Speaker 1: you use four pounds four to eight pounds in the
• 23:37
  Speaker 1: first month.
• 23:38
  Speaker 3: Do you get people like, can I have more? Can
• 23:41
  Speaker 3: I dose higher? Yes?
• 23:44
  Speaker 2: Absolutely, But when I explained to them that one of
• 23:47
  Speaker 2: the things we're trying to do is balance side effects
• 23:51
  Speaker 2: versus efficacy and remind them that, you know, the trials
• 23:56
  Speaker 2: of these medicines were only you know, in some cases
• 24:00
  Speaker 2: three weeks and in some cases fifty four weeks, and
• 24:03
  Speaker 2: they can be on these medicines as long as they
• 24:06
  Speaker 2: need to be to get to their goal, and it's
• 24:08
  Speaker 2: not a race to get to the goal. I think
• 24:10
  Speaker 2: that that helps people feel a lot more comfortable with
• 24:13
  Speaker 2: that rate of weight loss. We also talk a lot
• 24:16
  Speaker 2: about body composition and maintaining muscle mass while you're losing weight,
• 24:21
  Speaker 2: and it's much easier to maintain muscle mass if you
• 24:24
  Speaker 2: are not losing twenty pounds in a month.
• 24:26
  Speaker 3: Do you tell people just eat a lot of protein.
• 24:28
  Speaker 2: So getting enough protein in with these medications is important,
• 24:33
  Speaker 2: and so I do tell people, especially if their appetite
• 24:36
  Speaker 2: is very suppressed, to try to focus on getting protein
• 24:38
  Speaker 2: in first, but not necessarily only protein. The other key, though,
• 24:44
  Speaker 2: is doing resistance training while you're taking these medicines. Anyone
• 24:49
  Speaker 2: who loses a dramatic amount of weight, no matter how
• 24:52
  Speaker 2: they lose that weight, whether it's with one of these medications,
• 24:55
  Speaker 2: with weight loss surgery, with you know, more extreme dieting,
• 25:00
  Speaker 2: they will lose muscle. When you have less body weight,
• 25:04
  Speaker 2: it takes less muscle to move that body weight around.
• 25:09
  Speaker 2: That is just a fact of physics. But if you
• 25:14
  Speaker 2: just lose weight and you are not doing some resistance training,
• 25:18
  Speaker 2: you will lose more muscle. And if you are doing
• 25:23
  Speaker 2: resistance training, you can maintain more of that muscle because
• 25:26
  Speaker 2: you're actually using it.
• 25:28
  Speaker 1: This makes me think of the YouTube ad I got
• 25:30
  Speaker 1: last night about weight vests, like these things where you
• 25:34
  Speaker 1: wear a weighted vest during your workouts. And I think that,
• 25:37
  Speaker 1: going back to what I said before about the market,
• 25:39
  Speaker 1: that's actually something I'd like to go long in the
• 25:43
  Speaker 1: in the world that we can come back to this
• 25:44
  Speaker 1: investment idea at a later at a later time. So
• 25:48
  Speaker 1: can we briefly talk about logistics in terms of like
• 25:51
  Speaker 1: is it possible to get this and how much does
• 25:54
  Speaker 1: it cost? Because I think both of those have been
• 25:57
  Speaker 1: barriers people have talked about.
• 25:59
  Speaker 2: Yeah, So one of the things that is definitely true
• 26:02
  Speaker 2: is that the demand for these drugs has led to
• 26:05
  Speaker 2: intermittent supply issues and shortages. For a long time, people
• 26:10
  Speaker 2: would ask me, you know, which drug is the better drug?
• 26:12
  Speaker 2: Should I be on wig over your zep bound? And
• 26:15
  Speaker 2: my answer to them for a long time has been
• 26:17
  Speaker 2: the better drug is the drug you can get. And
• 26:21
  Speaker 2: at different times, in different markets, it has been one
• 26:25
  Speaker 2: or the other of the two. The challenge around cost
• 26:33
  Speaker 2: is a real one. One of the issues is that
• 26:36
  Speaker 2: the way that weight loss medicines are covered by insurance
• 26:40
  Speaker 2: is different than the way every other medication that you
• 26:42
  Speaker 2: take is covered by insurance. Your benefits manager has to
• 26:48
  Speaker 2: decide to opt in to a what is called an
• 26:52
  Speaker 2: anti obesity medication rider. So if your benefits administrator decides
• 26:59
  Speaker 2: that they want to opt into that rider, you may
• 27:02
  Speaker 2: you will likely have coverage for these medicines. And if
• 27:05
  Speaker 2: they've decided that they're not going to opt into that rider,
• 27:09
  Speaker 2: you will not have coverage for these medicines no matter
• 27:11
  Speaker 2: what you do, no matter what your unless you have
• 27:15
  Speaker 2: type two diabetes. So it used to be back in
• 27:19
  Speaker 2: the old days, like five years ago, that if somebody
• 27:23
  Speaker 2: had pre diabetes or signs of insulin resistance, some insurance
• 27:26
  Speaker 2: companies would cover the diabetes medicine for patients who did
• 27:30
  Speaker 2: not meet the criteria for diagnosing diabetes. But those days
• 27:34
  Speaker 2: are over. If you have anti obesity medication coverage, the
• 27:41
  Speaker 2: coverage is typically quite generous. I have a lot of
• 27:44
  Speaker 2: patients whose copays are in the neighborhood of twenty five
• 27:46
  Speaker 2: dollars a month. The list price for these medicines is
• 27:51
  Speaker 2: eleven to thirteen hundred dollars a month, so obviously that's
• 27:55
  Speaker 2: quite generous coverage. Both companies have pretty generous coupon offers
• 28:00
  Speaker 2: that knock down the price by about fifty percent, and
• 28:04
  Speaker 2: so then you're looking at something closer to five hundred
• 28:09
  Speaker 2: to six hundred dollars a month, prohibitive for many people,
• 28:12
  Speaker 2: no doubt, but better than eleven hundred dollars a month.
• 28:17
  Speaker 2: The challenge is that, you know, I've had patients switch insurance.
• 28:21
  Speaker 2: They get a new job, and they go to their
• 28:23
  Speaker 2: new job, and their old job had coverage for antiobesity
• 28:26
  Speaker 2: medications and their new job doesn't, and we're left scrambling
• 28:30
  Speaker 2: to kind of think through how to manage that.
• 28:33
  Speaker 1: So I have one more specific side effect question, which
• 28:37
  Speaker 1: is actually from my father, which is ozembic face a
• 28:42
  Speaker 1: real thing.
• 28:45
  Speaker 2: A lot of the side effects that people talk about
• 28:48
  Speaker 2: with these drugs has to do with rapid and extreme
• 28:52
  Speaker 2: weight loss and not with the medications themselves. So anyone
• 28:56
  Speaker 2: who loses a lot of weight very quickly will lose
• 29:00
  Speaker 2: weight in their face and gravity will take its course
• 29:04
  Speaker 2: and they will have sagging skin. That is true, not
• 29:08
  Speaker 2: just on your face. But on the rest of your body.
• 29:11
  Speaker 2: Younger people tend to do better with this. Their skin
• 29:14
  Speaker 2: is more elastic. Older people have less collagen and less elasticity,
• 29:20
  Speaker 2: and so their skin can't snap back as quickly. That
• 29:24
  Speaker 2: would be true if they have lost fifty pounds through
• 29:27
  Speaker 2: some other method as well. The other one that people
• 29:30
  Speaker 2: complain about a lot is hair loss. That is also
• 29:33
  Speaker 2: just a side effect of rapid weight loss. It is evolutionary.
• 29:37
  Speaker 2: There's not a lot to do about it, other than
• 29:40
  Speaker 2: to make sure that your vitamin replete as you're losing
• 29:43
  Speaker 2: weight so that you can grow new hair back. But
• 29:47
  Speaker 2: all of the side effects that people talk about specific
• 29:50
  Speaker 2: to these medicines, like ozenbic face and muscle loss are
• 29:56
  Speaker 2: all things that would happen if you had the same
• 29:59
  Speaker 2: degree of weight loss, regardless of how you did it.
• 30:03
  Speaker 1: So I want to talk about coming off the medications
• 30:05
  Speaker 1: because one of the things we hear a lot in
• 30:07
  Speaker 1: this discussion is this is forever, so we put you on.
• 30:11
  Speaker 1: When you start going on this, you should expect to
• 30:13
  Speaker 1: be on it forever. And that's partly, I think largely
• 30:16
  Speaker 1: because when we look at the trial data, when people
• 30:19
  Speaker 1: went off it, they regain a good share of the
• 30:22
  Speaker 1: weight quite quickly. And you talked about getting people to
• 30:26
  Speaker 1: their goal and then coming off it. Are people expecting
• 30:29
  Speaker 1: to be on for a year or two years, but
• 30:31
  Speaker 1: not expecting to be on forever.
• 30:32
  Speaker 3: So you talk about how you think about the other
• 30:35
  Speaker 3: side of this.
• 30:36
  Speaker 2: Yeah, absolutely so. I think the first thing we should
• 30:39
  Speaker 2: do is talk about that trial that said that everybody
• 30:42
  Speaker 2: who came off of it regained their weight. That was
• 30:45
  Speaker 2: a trial that was done by Novo Nordisk using wiggo
• 30:50
  Speaker 2: v or somemaglatide. They basically took the patients who had
• 30:55
  Speaker 2: been in the trial for FDA approval. Those patients were
• 30:59
  Speaker 2: all on the high dose of samaglatide, which is two
• 31:04
  Speaker 2: point four milligrams weekly, and they randomize those people to
• 31:08
  Speaker 2: either stay on two point four milligrams and continue to
• 31:12
  Speaker 2: have diet and lifestyle support, or to stop the medication
• 31:16
  Speaker 2: cold Turkey and also got no diet and lifestyle support.
• 31:22
  Speaker 2: It should not be surprising to anyone that the group
• 31:26
  Speaker 2: that stayed on the medication maintain their weight loss and
• 31:30
  Speaker 2: the group that stopped cold Turkey with no support started
• 31:33
  Speaker 2: to regain weight relatively quickly. I think it's also fair
• 31:39
  Speaker 2: to say that Novo Nordisk has a vested interest in
• 31:44
  Speaker 2: having people take these medications on a long term basis
• 31:49
  Speaker 2: and not necessarily providing the research to discuss an off ramp.
• 31:57
  Speaker 2: That has not been my experience. There are no sty
• 32:00
  Speaker 2: that say this is the method you should use to
• 32:02
  Speaker 2: take people off the medication. I have titrated people off
• 32:08
  Speaker 2: and down on these medications. In a few cases, people
• 32:12
  Speaker 2: were having such a good response to the medicine that
• 32:15
  Speaker 2: we were like, oh whoa, whoa, whoa, hold on, Like,
• 32:18
  Speaker 2: we got to go down quickly because you're losing too
• 32:21
  Speaker 2: much weight. But most people it's a really gentle downward titration,
• 32:28
  Speaker 2: similar to the titration we do to put people on
• 32:30
  Speaker 2: these medicines. The people who do the best coming off
• 32:35
  Speaker 2: of them, I find are the people who their lifestyle
• 32:41
  Speaker 2: was not the issue to begin with. So these are
• 32:46
  Speaker 2: often women who I mostly see women in my practice.
• 32:50
  Speaker 2: I would say my practice is ninety percent women. So
• 32:53
  Speaker 2: these are mostly women, often who have issues like polycystic
• 32:58
  Speaker 2: ovarian syndrome where they have struggled with weight for their
• 33:02
  Speaker 2: whole lives. Their diets were dialed in and they were exercising,
• 33:07
  Speaker 2: and so they really didn't make a lot of changes
• 33:11
  Speaker 2: when they went on the medications, they've achieved their goal weight,
• 33:16
  Speaker 2: and as they're titrating off the medication, they're just continuing
• 33:20
  Speaker 2: the same lifestyle that they already had when they started
• 33:23
  Speaker 2: the medications to begin with, those people tend to do
• 33:26
  Speaker 2: really well. Some people prefer to stay on a small dose,
• 33:32
  Speaker 2: and I have had patients who do things like stay
• 33:36
  Speaker 2: on the smallest dose, or they stay on the second
• 33:39
  Speaker 2: smallest dose, but they take it every ten days or
• 33:41
  Speaker 2: they take it every two weeks just to kind of
• 33:44
  Speaker 2: titrate themselves to kind of stay in their goal range
• 33:50
  Speaker 2: without taking the medicine on a weekly basis. But I've
• 33:54
  Speaker 2: also had patients come off. I've had patients come off
• 33:57
  Speaker 2: and beyond no medication. I've had some patients off and
• 34:00
  Speaker 2: choose to be on a small dose of something like
• 34:04
  Speaker 2: mat Foreman, which can help with weight maintenance and decrease
• 34:07
  Speaker 2: your risk of developing type two diabetes. Many of these
• 34:11
  Speaker 2: patients are risk of developing type two diabetes because of
• 34:14
  Speaker 2: their biochemistry and their genetics, and so there's lots of
• 34:18
  Speaker 2: different ways to do this, and I sort of approach
• 34:20
  Speaker 2: each patient differently.
• 34:29
  Speaker 1: More parent data, including how to talk to your doctor
• 34:32
  Speaker 1: about these drugs and how they relate to pregnancy and breastfeeding,
• 34:36
  Speaker 1: including whether they boost your fertility after the break. So
• 34:56
  Speaker 1: back to the New York Times Wellness section, a response
• 34:59
  Speaker 1: to how ubiquitous these drugs are is that we get
• 35:01
  Speaker 1: a lot of panic headlines. Sure, and last week we
• 35:04
  Speaker 1: saw a lot in the news right now about ozembic
• 35:06
  Speaker 1: being linked to vision loss.
• 35:08
  Speaker 3: Will ozempic make me go blind?
• 35:11
  Speaker 2: It is highly unlikely that ozempic is going to make
• 35:14
  Speaker 2: you go blind. It's good to know what you're referring
• 35:17
  Speaker 2: to is There was a study published in Jamma Ophisthalmology
• 35:23
  Speaker 2: that was done by some ophthalmologists at Harvard. What they
• 35:27
  Speaker 2: were looking at was an association between an extremely rare
• 35:34
  Speaker 2: cause of blindness called non argaritic anterior ischemic optic neuropathy
• 35:42
  Speaker 2: and patients taking somemagla type. And now they are a
• 35:48
  Speaker 2: huge referral center for this particular type of optic neuropathy,
• 35:54
  Speaker 2: and so they see a larger number of patients with
• 35:58
  Speaker 2: this problem. But in fact it's incredibly rare. It affects
• 36:03
  Speaker 2: typically two to ten people in out of every one
• 36:08
  Speaker 2: hundred thousand people, so it's very very rare, and what
• 36:13
  Speaker 2: they found was in patients who had been prescribed some maglaetide,
• 36:19
  Speaker 2: both for diabetes and for weight loss, that there was
• 36:23
  Speaker 2: an increase in the number of people who had this
• 36:27
  Speaker 2: particular type of optic neuropathy. However, even when you increase
• 36:34
  Speaker 2: something manyfold, if it is exceedingly rare like this is,
• 36:40
  Speaker 2: it will still be exceedingly rare. So a fourfold increase
• 36:46
  Speaker 2: in an exceedingly rare disease is still a tiny, tiny,
• 36:51
  Speaker 2: tiny number of people, and I have never seen this.
• 36:57
  Speaker 2: The authors also point out that they what they showed
• 37:00
  Speaker 2: was not a causal relationship, it was an association, and
• 37:07
  Speaker 2: they themselves said that they didn't know what a possible
• 37:12
  Speaker 2: mechanism for this would be. That they couldn't show that
• 37:15
  Speaker 2: there was a dose relationship, and they couldn't show that
• 37:20
  Speaker 2: if patients stopped the magnetide whether or not this would
• 37:24
  Speaker 2: get better or not. And those are all key things,
• 37:26
  Speaker 2: key key components to showing that a relationship between a
• 37:30
  Speaker 2: medication and a symptom are causal. So they really cannot
• 37:36
  Speaker 2: you really cannot say that themaglatide causes this type of
• 37:40
  Speaker 2: optic neuropathy, but rather there may be an association before
• 37:46
  Speaker 2: we get excited about this at all. We need a
• 37:49
  Speaker 2: lot more research into this, and it would not stop
• 37:53
  Speaker 2: me from prescribing these medications to people. Also, remember, not
• 37:58
  Speaker 2: taking these medications or stopping them can lead to other
• 38:04
  Speaker 2: much more common diseases like heart disease, high blood pressure, diabetes.
• 38:11
  Speaker 2: Those diseases are super common and make people sick every
• 38:15
  Speaker 2: single day. And so in my mind, the benefits of
• 38:19
  Speaker 2: some maglatide still far outweigh the risks of this particular
• 38:24
  Speaker 2: type of optic neuropathy.
• 38:26
  Speaker 1: So I want to come to pregnancy and breastfeeding briefly
• 38:29
  Speaker 1: because a lot of people ask about that. But it
• 38:31
  Speaker 1: strikes me how important you are to this conversation and
• 38:39
  Speaker 1: how valuable it is to have a provider who is
• 38:43
  Speaker 1: thinking carefully about how can I take what we know
• 38:48
  Speaker 1: from the science and work with the patients and think
• 38:50
  Speaker 1: about their constraints and what's going to work for them,
• 38:53
  Speaker 1: and so other than just seeing you, which is not
• 38:57
  Speaker 1: accessible to all people, I'm curious if there's like sort
• 39:01
  Speaker 1: of one or two takeaways you would give people about
• 39:05
  Speaker 1: either things to ask your provider or how to find
• 39:08
  Speaker 1: someone to treat you that is going to work with
• 39:12
  Speaker 1: you in the way that really is necessary to make
• 39:14
  Speaker 1: this as effective as possible.
• 39:17
  Speaker 2: I mean, I think the biggest thing I would look
• 39:20
  Speaker 2: for is I would look for someone who was treating
• 39:23
  Speaker 2: patients who struggle with weight and treating patients with diabetes
• 39:29
  Speaker 2: before this craze happened. So Ozempic was approved in early
• 39:35
  Speaker 2: twenty eighteen, and I started using it for weight loss
• 39:38
  Speaker 2: the week it was approved. And I have other colleagues
• 39:42
  Speaker 2: that I know who have a long history of experience
• 39:47
  Speaker 2: in treating patients with diabetes and insulin resistance, and they
• 39:52
  Speaker 2: were using those medicines before all this happened too. I
• 39:56
  Speaker 2: think there's been a lot of getting on the band
• 40:00
  Speaker 2: and look like there's a huge demand. I cannot blame
• 40:04
  Speaker 2: anyone who has gotten into this in the last couple
• 40:07
  Speaker 2: of years, but having a long experience with these medicines
• 40:13
  Speaker 2: and feeling comfortable with tit trading them would be the
• 40:17
  Speaker 2: number one question I would ask about.
• 40:20
  Speaker 3: That's great.
• 40:20
  Speaker 2: Unfortunately those people are rare, not always easy to come by,
• 40:25
  Speaker 2: but that would be what I would look for.
• 40:28
  Speaker 1: All right, let's talk about pregnancy and breastfeeding. So there
• 40:31
  Speaker 1: are actually two interesting questions. Well, the questions I have
• 40:35
  Speaker 1: about pregnancy and breastfeeding are a bit different. So most
• 40:38
  Speaker 1: people sort of accept the idea that we don't recommend
• 40:41
  Speaker 1: that you be on this during pregnancy, in part because
• 40:44
  Speaker 1: during pregnancy you are trying to gain weight and grow
• 40:46
  Speaker 1: another person. But we have found people who either are
• 40:50
  Speaker 1: trying to get pregnant or who are on this and
• 40:53
  Speaker 1: mistakenly get pregnant.
• 40:55
  Speaker 3: That seems to be more common than we might expect.
• 41:00
  Speaker 1: And I'm curious how much should we know about how
• 41:01
  Speaker 1: worried you should be if you were on this and
• 41:03
  Speaker 1: then you got pregnant, And is there any truth to
• 41:07
  Speaker 1: the idea that this.
• 41:07
  Speaker 3: Is like a magic fertility drug.
• 41:10
  Speaker 2: So as far as how worried you should be that
• 41:13
  Speaker 2: you're on the medication and you happen to get pregnant,
• 41:17
  Speaker 2: I would say the evidence doesn't really support that you
• 41:20
  Speaker 2: should panic these These medicines are not going to get
• 41:25
  Speaker 2: studied in pregnancy. A lot of the data that we're
• 41:27
  Speaker 2: going to get is going to be observational. There are
• 41:31
  Speaker 2: some studies of exenotide, which was the very first GLP
• 41:34
  Speaker 2: one in mice, and giving exenotide to mice that are pregnant,
• 41:41
  Speaker 2: and there were some issues around low birth weight and
• 41:47
  Speaker 2: that kind of thing. But it was all they really
• 41:50
  Speaker 2: found that. It was all related to the mouse is
• 41:52
  Speaker 2: intake of nutrition. And so if you're if you're on
• 41:56
  Speaker 2: this medicine and you get a positive pregnancy test and you're,
• 41:59
  Speaker 2: you know, four six weeks pregnant, and you stop the medication,
• 42:02
  Speaker 2: I wouldn't panic about that. I think probably things are
• 42:07
  Speaker 2: going to be just fine. The size of the molecules
• 42:13
  Speaker 2: suggests that it probably doesn't actually cross the plus senta
• 42:17
  Speaker 2: so easily. The issue is really around intake, and I
• 42:23
  Speaker 2: think most especially most American women, you know, we're usually
• 42:28
  Speaker 2: pretty well nourished going into pregnancy. We have some some
• 42:32
  Speaker 2: reserve that, you know, a couple of weeks is not
• 42:35
  Speaker 2: going to have a huge impact on the health of
• 42:37
  Speaker 2: a baby. I mean, the mice studies obviously they had
• 42:41
  Speaker 2: the mice on the drug whole time. They're in the
• 42:44
  Speaker 2: whole time, not for like a tiny fraction of the pregnancy.
• 42:48
  Speaker 2: So I definitely would not panic. There are a few
• 42:51
  Speaker 2: case reports out there at this point of people who
• 42:54
  Speaker 2: maybe didn't know they were pregnant until like late first
• 42:57
  Speaker 2: trimester or early second TRIMEU, and those case reports don't
• 43:02
  Speaker 2: show any significant issues.
• 43:05
  Speaker 3: All right, what about the fertility.
• 43:08
  Speaker 2: So the fertility thing is probably real, and I think
• 43:11
  Speaker 2: there's probably two different factors at play here. The first
• 43:16
  Speaker 2: thing is we know that insulin impacts ovarian function and
• 43:24
  Speaker 2: how frequently people ovulate, ovulation obviously being key to getting pregnant.
• 43:31
  Speaker 2: If you don't ovulate, you can't get pregnant. When you
• 43:34
  Speaker 2: improve people's insulin sensitivity, they ovulate more regularly, And there's
• 43:41
  Speaker 2: maybe some data and women with polycystic ovarian syndrome that
• 43:46
  Speaker 2: improved insulin sensitivity also improves equality. And so if you
• 43:51
  Speaker 2: are improving insulin sensitivity, which is one of the things
• 43:54
  Speaker 2: that these medications do and that weight loss can do
• 43:58
  Speaker 2: sort of generally, then you who may improve the frequency
• 44:03
  Speaker 2: and regularity with which a woman ovulates and improve equality.
• 44:09
  Speaker 2: And if you're doing both of those things, then you
• 44:11
  Speaker 2: will improve somebody's fertility. So that's one factor. The other
• 44:15
  Speaker 2: factor is with ters zeppetite specifically, so that's moonjar O
• 44:21
  Speaker 2: and zutbound. This has not necessarily been shown to be
• 44:25
  Speaker 2: true of the other medications like ozembic and wigov but
• 44:29
  Speaker 2: with chur zeppetite specifically, they have shown that with certain
• 44:35
  Speaker 2: lotos birth control pills. The way the medication affects how
• 44:40
  Speaker 2: the birth control pill moves through your GI tract can
• 44:46
  Speaker 2: delay its absorption. And if that's the case and you're
• 44:50
  Speaker 2: not super careful about taking your birth control pill regularly,
• 44:55
  Speaker 2: you could have a enough of a drop and the
• 44:58
  Speaker 2: levels of the hormones and the birth control pill that
• 45:00
  Speaker 2: would allow you to ovulate, and then that would obviously
• 45:04
  Speaker 2: allow you to get pregnant. The key there is really
• 45:08
  Speaker 2: taking and then you should do this all the time anyway,
• 45:10
  Speaker 2: but taking your birth control pill at the exact same
• 45:13
  Speaker 2: time every single day, and it may be helpful in
• 45:17
  Speaker 2: this case to take it on an empty stomach. And
• 45:19
  Speaker 2: if you're really worried to use a different method of contraception, we.
• 45:22
  Speaker 1: Have many, there are many good we have so many.
• 45:27
  Speaker 1: So what about breastfeeding? So people have the baby, they
• 45:33
  Speaker 1: want to lose weight?
• 45:34
  Speaker 3: Is it okay?
• 45:37
  Speaker 2: So we don't have any data one way or the other.
• 45:40
  Speaker 2: So there's not really much to hang your hat on here.
• 45:44
  Speaker 1: Is this a place you think we'll get data? Because
• 45:46
  Speaker 1: I think it absolutely will not in pregnancy. No one's
• 45:48
  Speaker 1: on purpose going to be giving this a pregnant women.
• 45:50
  Speaker 1: Do you think we'll get it in breastfeeding.
• 45:53
  Speaker 2: I think we probably will. I think that there's a
• 45:56
  Speaker 2: couple of ways, a couple of things that are helpful
• 45:59
  Speaker 2: to know. So in animal studies they did find exenotide,
• 46:06
  Speaker 2: so again that was the oldest GLP one. They did
• 46:08
  Speaker 2: find exenotide in breast milk in animal studies. The thinking
• 46:15
  Speaker 2: is is that semaglatide, which is one of the you know,
• 46:19
  Speaker 2: which is ozenbic, that the molecule is large enough that
• 46:23
  Speaker 2: the amount that would get into breast milk would be
• 46:26
  Speaker 2: relatively small. But the other thing I think is really
• 46:30
  Speaker 2: important to remember is what I said about the oral
• 46:33
  Speaker 2: absorption of these medications earlier. So we only absorb a
• 46:37
  Speaker 2: tiny fraction of what enters our GI tract. So if
• 46:42
  Speaker 2: you have a tiny amount of samaglatide in your breast
• 46:45
  Speaker 2: milk and then your baby drinks your breast milk, then
• 46:49
  Speaker 2: the baby gets samglatide in their gi tract, but they're
• 46:53
  Speaker 2: only going to absorb up to one percent of it.
• 46:56
  Speaker 2: That the exposure that the baby has to the drug
• 47:02
  Speaker 2: is vanishingly small. And in fact, you know, some of
• 47:06
  Speaker 2: the databases that you know talk about the safety of
• 47:10
  Speaker 2: medications and breastfeeding say that samaglatide is probably safe in
• 47:15
  Speaker 2: breastfeeding for all of those reasons. If breastfeeding is really
• 47:20
  Speaker 2: a goal of yours and is really important to you,
• 47:22
  Speaker 2: the bigger issue is actually the impact that the change
• 47:26
  Speaker 2: in nutrition and the change in hydration it may have
• 47:31
  Speaker 2: on breast milk supply. And so I do always warn
• 47:33
  Speaker 2: people about that because some women's bodies and breast milk
• 47:39
  Speaker 2: supply will be more sensitive to changes in calorie intake
• 47:44
  Speaker 2: than others. And so you know, I don't want somebody
• 47:48
  Speaker 2: to be disappointed because you know, they decided to go
• 47:50
  Speaker 2: on one of these medicines and it like take their supply.
• 47:53
  Speaker 2: I'm more worried about that. I do think as babies
• 47:57
  Speaker 2: get bigger and more resilient, it's also a little easier
• 48:02
  Speaker 2: to sort of think about these things as well. And
• 48:05
  Speaker 2: so you know, maybe you don't want to go on
• 48:08
  Speaker 2: some magletide like the week you come home from the hospital.
• 48:12
  Speaker 1: But if we're asking, like I'm still breastfeeding eighteen month
• 48:14
  Speaker 1: old one I'm at night, maybe like this is not
• 48:17
  Speaker 1: a major consideration for that.
• 48:19
  Speaker 2: Yeah, I think the amount of breastfeeding that's going on,
• 48:22
  Speaker 2: the age of the baby, all those things are factors
• 48:24
  Speaker 2: in this conversation, and ultimately I would ultimately I would argue,
• 48:29
  Speaker 2: we should give ourselves a little time and grace after
• 48:32
  Speaker 2: we have a baby, before we start worrying about these things.
• 48:35
  Speaker 2: But again, if it's an eighteen month old comfort nursing
• 48:39
  Speaker 2: at night and in the morning, like, that's a very
• 48:41
  Speaker 2: different conversation than someone who's exclusively breastfeeding a four week old.
• 48:47
  Speaker 1: I always find it so much easier in some ways
• 48:48
  Speaker 1: to answer these questions about breastfeeding than about pregnancy, because
• 48:51
  Speaker 1: you could say, look, we can look in the breast milk,
• 48:53
  Speaker 1: like yeah, Like with pregnancy, it's like it's the placenta.
• 48:57
  Speaker 1: It's this like how much is absorbing. It's a very
• 48:59
  Speaker 1: complicated system. We kind of can't get into. This is like, well,
• 49:02
  Speaker 1: they're consuming it, so we can just take it out
• 49:04
  Speaker 1: and look at it and then we can answer.
• 49:08
  Speaker 2: One of the things that's super interesting that they have
• 49:10
  Speaker 2: done is they have done perfusion studies with GLP ones
• 49:13
  Speaker 2: and placentas, huh, or they have put GLP one in.
• 49:19
  Speaker 2: I mean, this is obviously all like experimental, like when
• 49:22
  Speaker 2: the placenta is no longer in a good creature's body,
• 49:27
  Speaker 2: But so you can actually they've done studies where they
• 49:30
  Speaker 2: perfuse the maternal side of the placenta with something that
• 49:33
  Speaker 2: contains a GLP one and then try to measure the
• 49:36
  Speaker 2: GLP one on the fetal side of the placenta.
• 49:39
  Speaker 3: That's cool.
• 49:40
  Speaker 2: A little bit gets across, but not very much. But
• 49:44
  Speaker 2: you know, when you're thinking about systems in which to
• 49:46
  Speaker 2: kind of study these things, I think it's kind of interesting.
• 49:49
  Speaker 3: The placenta is so it's like a whole other podcast.
• 49:51
  Speaker 1: The placenta is so interesting, just like it's such an
• 49:54
  Speaker 1: interesting organ it is.
• 49:55
  Speaker 2: It's a it's also a gland. It's a hormone gland.
• 49:58
  Speaker 2: It makes all kinds of interesting hormonesspective.
• 50:02
  Speaker 1: Podcast with Jillian will be like details about the placenta.
• 50:06
  Speaker 3: So you prescribe a lot of these drugs. You think
• 50:10
  Speaker 3: a lot about this.
• 50:12
  Speaker 1: If you had to summarize the experience of the people
• 50:16
  Speaker 1: that you treat with this, how would you describe it?
• 50:19
  Speaker 2: Life changing? I've written thousands, probably tens of thousands of
• 50:25
  Speaker 2: prescriptions for these medicines over the last twenty years, and
• 50:31
  Speaker 2: that is probably the most commonly used phrase to describe
• 50:36
  Speaker 2: how people feel about these medications.
• 50:47
  Speaker 3: Thank you so much.
• 50:48
  Speaker 1: I feel like this was incredibly helpful in just understanding
• 50:53
  Speaker 1: the landscape, so I really appreciate it.
• 50:56
  Speaker 3: Thanks for being here.
• 50:56
  Speaker 2: Oh it's my pleasure.
• 51:14
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• 51:17
  Speaker 1: the parent Data team and PI Rex. If you have
• 51:20
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• 51:39
  Speaker 3: For example, Jillian has actually.
• 51:41
  Speaker 1: Written out a lot of what she talked about today
• 51:43
  Speaker 1: in an article titled appropriately ozembic Manjaro Rigovi Oh my
• 51:49
  Speaker 1: yes exclamation point at the end of that that dives
• 51:52
  Speaker 1: even more into the numbers, and you can read that
• 51:54
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  Speaker 3: Penelte, write mom, We'll see you next time.