Emily Oster

17 min Read Emily Oster

News about weight-loss drugs is hard to miss. A new generation of drugs — Ozempic, Wegovy, Mounjaro, Zepbound — are on television, on billboards, and in many of our homes. There is little debate about the efficacy of the drugs for weight loss (they work, at least for most people) but lots of discussion about everything else surrounding them. 

What I’ve found missing from this conversation is the answer to the practical questions I think many people would like to ask their doctors. Are these drugs right for me? How do the side effects work? How fast would I lose weight? Do I really have to take them forever? What if I’m breastfeeding?  

Today I brought on Dr. Gillian Goddard to talk about this. She’s an endocrinologist in private practice, and she writes our Hot Flash newsletter (sign up on your Account page!), all about the post-reproductive years. Gillian has been prescribing these drugs for many years, and she’s extremely thoughtful about who is a good candidate and who isn’t. I learned a lot here, as I always do from Gillian, and I’m sure you will too. 

Here are three highlights from the conversation:

How are the effects of these weight-loss drugs different from what was offered in the past?

Emily Oster:

There have been other weight-loss drugs in the past, some of which have turned out to be terrible for you, but most of which have turned out not to work. In a sense, the big delta here feels to me like when you talk to people about being on one of these medications for weight loss, they will talk about it as a very big sea change in how they are experiencing food and fullness, which feels very different than the way people would talk about some of the older kinds of medications. First of all, is that consistent with your experience? And if yes, do we have a sense of why this is so different?

Dr. Gillian Goddard:

Yeah, I would say that’s definitely consistent with my experience. When I first started in my practice, the options were really some old-fashioned amphetamine-based pills that suppressed your appetite and made you feel a little jittery.

Emily:

Mother’s little helper, I think is what those were called in the 1950s, literally.

Gillian:

That’s right. And they’ve been around since the 1950s. But they had a lot of side effects. People couldn’t sleep after they took them. They also didn’t work for very long. They’re still around and you can give them to people, and they will suppress people’s appetite and they will make them feel a little zingy, but they don’t work very long. After two months, people’s appetite starts to come back. They start to regain the weight that they’ve lost. And most of us need more than a two-month jump-start if we’re really going to have any impact, to get significant weight loss. There have been some other weight-loss medicines over the years that worked in different ways. We used bupropion, which is Wellbutrin for weight loss, which sometimes would help people with cravings, but there really hasn’t been anything that’s as effective as this class of medications is.

The kind of weight loss we see with this class of medicines is more akin to the weight loss people see with bariatric surgery than it is to the weight loss that people saw in the past with older weight-loss medications. So they really are paradigm-shifting. Why? There’s a lot of reasons why. For one thing, we’re really starting to understand that a lot of what gets in people’s way as far as losing weight is not appetite. It’s not appetite, and it’s not what they’re eating; it’s how their body is processing what they’re eating. If somebody’s not processing carbohydrates well and that’s impacting how they’re storing carbohydrates and we can change how they’re processing carbohydrates so that they’re processing them more typically, then all of a sudden, we can have a big impact.

The other thing that we’re really starting to understand is that GLP-1 [the drug] and the hormone insulin actually have effects in the brain around satiety, around the reward system, and around metabolic rate. All these things are really closely linked, and so when you give someone GLP-1, you raise their GLP-1 levels in their brain and you decrease the insulin levels in their brain, and that will have big impacts on things like “food noise” and the reward people feel from consuming something super-salty and crunchy or sugary.

Who is a good candidate for these drugs?

Emily:

I’d love to talk about your experience using this with your patients. How do you evaluate whether someone is a good candidate? Someone comes in to see you, they say: I heard about this drug, I want it. How do you think about whether that’s a good idea?

Gillian:

There’s a few things that I take into consideration when I think about this. My first thing that I think about is, what have they tried to lose weight in the past and how successful have they been with those methods? I will tell you, usually by the time someone comes to see me, they have tried everything. They’ve been on every diet, they have done extreme dieting, they’ve done keto, they’ve done… literally, you name it, they’ve done it. They’ve tried every type of exercise. They may have tried other medications in the past and they may have had short-term success with those things, but they’ve never been able to maintain the loss that they achieved. I’ve had many patients come in who’ve already had bariatric surgery too and have regained the weight that they lost with bariatric surgery. These are not people who have just decided on a whim that they need to lose 10 pounds because they’re feeling a little uncomfortable. These are often people who’ve had lifelong struggles with weight and they’ve literally tried everything.

Emily:

Do you think about a BMI cutoff, or is there an amount of weight that people would need to lose that would influence whether you think someone was a good candidate?

Gillian:

That’s a tricky question, because I hate BMI as a measure to apply to an individual.

Emily:

That’s why I changed what I was saying, but I agree. BMI is a problematic metric.

Gillian:

BMI is an incredibly problematic metric, but we do have to take it into account because it is the metric that the insurance company uses to decide whether or not they’re going to cover the medication, and these medications are expensive. So while I don’t necessarily have a BMI cutoff that I am looking at, and I don’t use BMI as a way to set a weight-loss goal for a patient, we do have to at least look at the BMI and know what it is when we’re thinking about getting coverage for the patient for these medications.

I look much more holistically at a patient who’s coming in to see me. I want to know what their blood sugar levels look like, what their insulin levels look like. Are they having blood pressure problems? Are they on cholesterol medication? Are they having problems with mobility because of weight?

I really care much more about how weight is impacting someone’s broader health when I think about these medications, because there’s data that shows that just having a high BMI in and of itself is not the problem. The problem is when the weight is associated with other medical problems. And that’s where I like to focus my efforts and goals too.

How do drugs like Ozempic impact pregnancy and fertility?

Emily:

Let’s talk about pregnancy and breastfeeding. There are actually two interesting questions. Well, the questions I have about pregnancy and breastfeeding are a bit different. Most people accept the idea that we don’t recommend that you be on this during pregnancy, in part because during pregnancy you are trying to gain weight and grow another person, but we have found people who either are trying to get pregnant or who are on this and mistakenly get pregnant. That seems to be more common than we might expect. And I’m curious, how much should we know about how worried you should be if you were on this and then you got pregnant, and is there any truth to the idea that this is like a magic fertility drug?

Gillian:

As far as how worried you should be that you’re on the medication and you happen to get pregnant, I would say the evidence doesn’t really support that you should panic. These medicines are not going to get studied in pregnancy. A lot of the data that we’re going to get is going to be observational. There are some studies of exenatide, which was the very first GLP-1 in mice, and giving exenatide to mice that are pregnant. There were some issues around low birth weight and that kind of thing, but they really found that it was all related to the mouse’s intake of nutrition. So if you’re on this medicine and you get a positive pregnancy test and you’re four, six weeks pregnant and you stop the medication, I wouldn’t panic about that. I think probably things are going to be just fine. The size of the molecule suggests that it probably doesn’t actually cross the placenta so easily.

The issue is really around intake, and I think especially most American women, we’re usually pretty well nourished going into pregnancy. We have some reserve that a couple of weeks is not going to have a huge impact on the health of a baby. The mice studies, obviously they had the mice on the drug through the whole time, not for a tiny fraction of the pregnancy. So I definitely would not panic. There are a few case reports out there at this point of people who maybe didn’t know they were pregnant until late first trimester or early second trimester, and those case reports don’t show any significant issues.

Emily:

All right. What about the fertility?

Gillian:

The fertility thing is probably real, and I think there’s probably two different factors at play here. The first thing is we know that insulin impacts ovarian function and how frequently people ovulate, ovulation obviously being key to getting pregnant. If you don’t ovulate, you can’t get pregnant. When you improve people’s insulin sensitivity, they ovulate more regularly. And there’s maybe some data in women with polycystic ovary syndrome that improved insulin sensitivity also improves egg quality. So if you are improving insulin sensitivity, which is one of the things that these medications do and that weight loss can do sort of generally, then you may improve the frequency and regularity with which a woman ovulates and improve egg quality. If you’re doing both of those things, then you will improve somebody’s fertility. That’s one factor.

The other factor is with tirzepatide specifically, so that’s Mounjaro and Zepbound. This has not necessarily been shown to be true of the other medications, like Ozempic and Wegovy. But with tirzepatide specifically, they have shown that with certain low-dose birth control pills, the way the medication affects how the birth control pill moves through your GI tract can delay its absorption. If that’s the case and you’re not super-careful about taking your birth control pill regularly, you could have enough of a drop in the levels of the hormones in the birth control pill that would allow you to ovulate and then that would obviously allow you to get pregnant. The key there is really taking — and you should do this all the time anyway — but taking your birth control pill at the exact same time every single day. It may be helpful in this case to take it on an empty stomach and, if you’re really worried, to use a different method of contraception.

Full transcript

This transcript was automatically generated and may contain small errors.

Emily Oster:

If you listen to the news, you hear a lot about Ozempic. It’s actually been around for a couple of decades, but only in the last couple of years, it feels like it’s everywhere all the time.

We often use Ozempic as a shorthand for a broader class of GLP-1 drugs. They’re also called semaglutide, but you may have heard of Wegovy, Manjaro, Rybelsus, Zepbound. Broadly, these all do roughly the same thing, which is that they treat type-two diabetes and they help people lose weight. So much of the discussion in popular culture about this is about these big picture social questions around these drugs. What are the societal implications of all of these drugs becoming available and helping so many people lose so much weight? How does this change our relationship to the food system? How does this change the stock market price for Nabisco? How should we think about body positivity and the way we think about weight, and how that relates to these new options for weight loss? 

But today I wanted to talk about a narrower question, and one I think many people ask, which is, are these drugs right for me? And so I invited an endocrinologist to address this smaller picture. You might remember Doctor Gillian Goddard from the episode on perimenopause and birth control later in life. She writes our newsletter, Hot Flash, which you should be subscribed to immediately, I love it. And today she and I are going to talk about GLP-1 drugs. We’re going to talk about how she prescribes them as an endocrinologist, about who is a good candidate for these, and about how the findings from trials do and do not translate into the way she uses these drugs in her patients.

I was interested to ask her, how do you get people on the drugs? What kind of side effects do they experience? Do they come off the drugs? Do you find that people have to take these forever? I’m hoping that this conversation will be the path to a conversation that you could have with your doctor, if this is something that feels right for you. If you’re curious about the drugs yourself, or just generally interested in what feels like an inescapable phenomenon, this is the episode for everything you want to know about Ozempic, but have no one to ask it to. 

And before we get going, I want to be clear: these drugs are not for everyone. Plenty of people have no interest in them at all, and we’re certainly not here to talk anyone into anything. But the drugs are here, probably to stay, and I think it is important to understand how they work. 

After the break, our own doctor, Gillian Goddard.

Emily Oster:

Dr. Gillian Goddard. Thank you for coming back to ParentData.

Dr. Gillian Goddard:

I’m so excited to be back.

Emily Oster:

You write for ParentData, you write our newsletter called The Hot Flash, and you’re an endocrinologist. Can you tell us what that is?

Dr. Gillian Goddard:

Sure. I’m an adult endocrinologist, which means that I take care of people who are having problems with their hormones and the glands that make those hormones. My typical patients will have problems like thyroid problems or reproductive problems or diabetes. Those are the most common things that I see in my practice.

Emily Oster:

And how would I know that I need to see an endocrinologist?

Dr. Gillian Goddard:

Sometimes it’s really challenging to know when you need to see an endocrinologist, and there’s not very many of us. There’s less than 9,000 practicing endocrinologists in the United States. So, sometimes even if you need to see an endocrinologist, it’s not the easiest thing to accomplish. But I think that the things that tend to send people to see me are things like not having regular periods and their gynecologist has done some workup and they can’t seem to figure out why or having problems with blood sugar or I see a lot of people who are struggling with their weight and it’s having impacts on their health.

Emily Oster:

That last piece is what we’re going to talk about today. I want to have a conversation about semaglutides, Ozempic, Zepbound, Mounjaro, Wegovy whatever is the name of the thing you are hearing about. I think this is an important conversation because we hear about these all the time. If I had to categorize the New York Times Well section of late, it’s just literally a list of articles about Ozempic and every third one, then they’ll be like, oh, also should you drink raw milk? And then we’re just back to Ozempic, don’t drink raw milk.

Many of those articles are either about a new study which says Ozempic also fixes this problem that a lot of people have, or it is a big picture question about how society is going to change with the result of Ozempic. And some of these are quite interesting as an economist. So, people are talking about are we headed for a collapse of the snack food market and should you short Doritos in the stock market or go long Peloton or whatever it is, short Peloton. I don’t know. Economics is complicated, but the conversation I want to have today is about being a doctor, treating Ozempic on a much lower level because that’s something that you do a lot. Correct?

Dr. Gillian Goddard:

I do it a lot, all day every day.

Emily Oster:

So, let’s start with the most basic question in case people are not reading every third article in the New York Times Well section. Tell me about these drugs and why there is so much discussion of them.

Dr. Gillian Goddard:

Sure. Most of these drugs are in a class called GLP-1 agonist. GLP-1 is a hormone that we all have in our bodies and it impacts how our bodies produce insulin, how our bodies respond to insulin and how we metabolize sugar. They’re not new drugs. The first GLP-1 was approved by the FDA in 2004, and they were originally developed to treat type two diabetes and they’re very effective treatments for type two diabetes. Over the last 20 years, as is likely to happen in a big market, the class has gotten very crowded. There are many, many GLP-1s and started exploring other uses for them. Semaglutide, which is Ozempic and Wegovy, is actually not the first GLP-1 that was approved for use for weight loss. The first GLP-1 that was approved for use for weight loss was liraglutide and it was approved in 2014. So, this idea is not new at all. And in fact, endocrinologists have been using GLP-1 agonists off-label to help people lose weight since they were approved in 2004.

What’s different is how effective these medicines are and how frequently they have to be given. The very first GLP-1 exenatide was a twice daily injection and that was difficult to get even type two diabetics to do. Semaglutide and tirzepatide, so semaglutide again is Ozempic and Wegovy. Tirzepatide is Mounjaro and Zepboud. Those medicines are once weekly medicines.

Emily Oster:

But it’s still an injection.

Dr. Gillian Goddard:

They’re still an injection. There’s one oral GLP-1 agonist, it’s semaglutide and the brand name is Rybelsus and it’s not approved for weight loss. It’s only approved for treating type two diabetes so far.

Emily Oster:

I want to talk a little bit about the sort of dosing and treatment just so people understand the landscape. Obviously, people would prefer to take this in a pill. Why are we not all taking it in a pill?

Dr. Gillian Goddard:

Only about 1% of the drug is absorbed if you just… If you just orally took semaglutide, only about 1% of what you put in your mouth would be absorbed through your gastrointestinal system, so super inefficient. It took them the better part of the first 15 years these drugs were on the market to come up with a pill. The pill that is available, which is Rybelsus, you have to take that pill first thing in the morning on an empty stomach with not more than half a cup of water. You have to wait 30 minutes and then you can have something to eat or drink at that point. So, there’s lots of room for user error, but it’s conceivable that Rybelsus in large enough doses to impact weight or some other form of these medicines that’s oral will come out in the future. I would just say at this point we can’t get enough of these drugs into you through a pill to have them be particularly effective for weight loss.

Emily Oster:

So, people have injections, you can do the injection yourself at home.

Dr. Gillian Goddard:

It’s super easy. Most of the products that are specifically for treating obesity are in single use auto-injectors. They look a lot like an EpiPen.

Emily Oster:

Okay. There have been other weight loss drugs in the past, some of which have turned out to be terrible for you, but most of which have turned out not to work. In a sense, the big delta here feels to me like when you talk to people about being on one of these medications for weight loss, they will talk about it as a very big C change in how they are experiencing food and fullness, which feels very different than the way people would talk about some of the older kinds of medications. First of all, is that consistent with your experience? And if yes, do we have a sense of why this is so different?

Dr. Gillian Goddard:

Yeah, I would say that’s definitely consistent with my experience. When I first started in my practice, the options were really some old-fashioned amphetamine based pills that suppressed your appetite and made you feel a little jittery.

Emily Oster:

Mother’s little helper I think is what those were called in the 1950s, literally.

Dr. Gillian Goddard:

That’s right. And they’ve been around since the 1950s. But they had a lot of side effects. People couldn’t sleep after they took them. They also didn’t work for very long. They’re still around and you can give them to people and they will suppress people’s appetite and they will make them feel a little zingy, but they don’t work very long. After two months, people’s appetite starts to come back. They start to regain the weight that they’ve lost, and most of us need more than a two month jumpstart if we’re really going to have any impact to get significant weight loss. There have been some other weight loss medicines over the years that worked in different ways. We used bupropion, which is also Wellbutrin for weight loss, which sometimes would help people with cravings, but there really hasn’t been anything that’s as effective as this class of medications is.

The kind of weight loss we see with this class of medicines is more akin to the weight loss people see with bariatric surgery than it is to the weight loss that people saw in the past with older weight loss medications. So, they really are paradigm shifting. Why? There’s a lot of reasons why. For one thing, we’re really starting to understand that a lot of what gets in people’s way as far as losing weight is not appetite. It’s not appetite and it’s not what they’re eating, it’s how their body is processing what they’re eating. If somebody’s not processing carbohydrates well and that’s impacting how they’re storing carbohydrates and we can change how they’re processing carbohydrates so that they’re processing them more typically, then all of a sudden, we can have a big impact.

The other thing that we’re really starting to understand is that GLP-1, the hormone and insulin actually have effects in the brain around satiety, around the reward system and around metabolic rate. All these things are really closely linked, and so when you give someone GLP-1, you raise their GLP-1 levels in their brain and you decrease the insulin levels in their brain and that will have big impacts on things like food noise and the reward people feel from consuming something super salty and crunchy or sugary.

Emily Oster:

Let’s turn to the prescribing behavior here because I’d love to talk about your experience using this with your patients. How do you evaluate whether someone is a good candidate? Someone comes in to see you, they say, I heard about this drug, I want it. How do you think about whether that’s a good idea?

Dr. Gillian Goddard:

There’s a few things that I take into consideration when I think about this. My first thing that I think about is what have they tried to lose weight in the past and how successful have they been with those methods? I will tell you, usually by the time someone comes to see me, they have tried everything. They’ve been on every diet, they have done extreme dieting, they’ve done keto, they’ve done… Literally, you name it, they’ve done it. They’ve tried every type of exercise. They may have tried other medications in the past and they may have had short-term success with those things, but they’ve never been able to maintain the loss that they achieved. I’ve had many patients come in who’ve already had bariatric surgery too and have regained the weight that they lost with bariatric surgery. These are not people who have just decided on a whim that they need to lose 10 pounds because they’re feeling a little uncomfortable. These are often people who’ve had lifelong struggles with weight and they’ve literally tried everything.

Emily Oster:

Do you think about a BMI cutoff, is there an amount of weight that people would need to lose that would influence whether you think someone was a good candidate?

Dr. Gillian Goddard:

That’s a tricky question because I hate BMI as a measure to apply to an individual.

Emily Oster:

That’s why I used amount of weight. I changed what I was saying, but I agree. BMI is a problematic metric.

Dr. Gillian Goddard:

BMI is an incredibly problematic metric, but we do have to take it into account because it is the metric that the insurance company uses to decide whether or not they’re going to cover the medication, and these medications are expensive. So, while I don’t necessarily have A BMI cutoff that I am looking at, and I don’t use BMI as a way to set a weight loss goal for a patient, we do have to at least look at the BMI and know what it is when we’re thinking about getting coverage for the patient for these medications. I look much more holistically at a patient who’s coming in to see me. I want to know what their blood sugar levels look like, what their insulin levels look like. Are they having blood pressure problems? Are on cholesterol medication? Are they having problems with mobility because of weight?

I really care much more about how weight is impacting someone’s broader health when I think about these medications, because there’s data that shows that just having a high BMI in and of itself is not the problem. The problem is when the weight is associated with other medical problems. And that’s where I like to focus my efforts and goals too.

Emily Oster:

Do you have people who come in who just say, I’d really like to lose this extra 15 pounds so I can fit into this dress from my high school years or from… for very legitimate reasons, which is many of us maybe would like to lose an extra 10 pounds. I assume you see patients with that request.

Dr. Gillian Goddard:

I do. My office is on the Upper East Side of Manhattan.

Emily Oster:

What do you say? I didn’t quite put myself in this category, but I can certainly see personally the instinct to be like, boy, maybe I’d run faster if I was a little… I can see the instinct. So, I’m curious how you counsel in that situation because it sounds like your answer would be no, but there must be something beyond no.

Dr. Gillian Goddard:

Yeah, I mean I would never just tell a patient no because I don’t think that’s a very effective way to communicate what my concerns are, which would be these medicines are not a quick fix. I tell patients to expect to be on them for a minimum of a year and they’re changing other things about how your body is functioning and working that I think you might not want to change and might have some unintended consequences if you’re really just looking to lose 10 or 15 pounds. You mentioned athletic performance, I always really caution people who part of their goal is to improve athletic performance because that’s actually a real challenge with these medications. The way these medications impact appetite and metabolism can actually, in some cases, adversely affect people’s athletic performance. So, anytime I have someone come in who’s whether they’re more professional about it or an amateur who really cares about their athletic performance, I always talk very carefully with them about the pros and cons of these medicines because it can actually backfire. It can really adversely affect performance.

Emily Oster:

That’s good to know. Someone comes in, you decide that for various reasons looking holistically, you’re going to start on these medications. In the trials for these drugs, the way that trials work is you just dose one dose, so you have a trial of a dose, there’s the dose of this, everyone gets that and that’s the dose because when you are trying to show scientific evidence that something works, you can’t be messing about with how much people are getting to optimize for each individual. You need to be able to show, we gave everybody this number of milligrams this frequently and then in the end the result was this. That’s how you get your FDA approval. But in your office, that’s not often how medicine works. I assume you do not start everybody on exactly the dose that was in the trial. So, I’m curious how you navigate that beginning of this process with someone and why you would not, maybe you can articulate better than I can, why you would not just go in with the trial dosage and that’s what it is.

Dr. Gillian Goddard:

That is actually a really tricky thing with these medicines. With Wegovy specifically, they had a very strict titration in the trial that involved going up on the medication every single month until they were on the target dose. And if patients couldn’t tolerate that, they had to drop out of the trial. And that trial actually had a very high rate of patients dropping out for side effects from the medication, about 15%. So, I try not to dose the medications in that way. We always start with the lowest dose with these medications. There’s a starting dose with all of them. And then my goal is actually to titrate to a rate of weight loss of about one to two pounds per week on average. I know when you read in the media about people taking these medicines, they will say, I lost 20 pounds in the first month. That is not my goal for people.

My goal is one to two pounds a week on average and I have them stay on a dose that gets them a rate of weight loss in that range until it stops working. So, many of my patients will stay on much lower doses. And my goal with that is twofold. One is I think that’s a much more sustainable rate of loss. I think it’s easier to minimize muscle loss when people are not losing weight so rapidly. It also minimizes side effects. So, the other thing you will hear a lot about with these medications is people saying that they are throwing up all the time. They’re super, super sick. I always tell my patients, you should never be throwing up. You may be nauseated at times, especially within the first 48 hours of taking the dose, but you should never be throwing it up. And if you’re throwing up, I want you to call me and let me know because that means we need to make a change. So, a more gentle upward titration can allow us to balance the benefit with some of the side effects of these medications.

Emily Oster:

Do you find people are happy with the one to two? If I come in with the expectation, I’m going to lose 20 pounds in the first month and then you tell me your expectation should be that you use four pounds, four to eight pounds in the first month, do you get people who are like, can I have more? Can I dose higher?

Dr. Gillian Goddard:

Yes, absolutely. But when I explain to them that one of the things we’re trying to do is balance side effects versus efficacy and remind them that the trials of these medicines were only in some cases 23 weeks and in some cases 54 weeks and they can be on these medicines as long as they need to be to get to their goal, and it’s not a race to get to the goal. I think that that helps people feel a lot more comfortable with that rate of weight loss. We also talk a lot about body composition and maintaining muscle mass while you’re losing weight and it’s much easier to maintain muscle mass if you are not losing 20 pounds in a month.

Emily Oster:

Do you tell people just eat a lot of protein?

Dr. Gillian Goddard:

Getting enough protein in with these medications is important. So, I do tell people, especially if their appetite is very suppressed to try to focus on getting protein in first, but not necessarily only protein. The other key though is doing resistance training while you’re taking these medicines. Anyone who loses a dramatic amount of weight, no matter how they lose that weight, whether it’s with one of these medications, with weight loss surgery, with more extreme dieting, they will lose muscle. When you have less body weight, it takes less muscle to move that body weight around. That is just a fact of physics. But if you just lose weight and you are not doing some resistance training, you will lose more muscle. And if you are doing resistance training, you can maintain more of that muscle because you’re actually using it.

Emily Oster:

This makes me think of the YouTube ad I got last night about weight vests. These things where you wear a weighted vest during your workouts. And I think that going back to what I said before about the market, that’s actually something I’d like to go long in in the world. We can come back to this investment idea at a later time.

Can we briefly talk about logistics in terms of is it possible to get this and how much does it cost? Because I think both of those have been barriers people have talked about.

Dr. Gillian Goddard:

One of the things that is definitely true is that the demand for these drugs has led to intermittent supply issues and shortages. For a long time, people would ask me, which drug is the better drug? Should I be on Wegovy or Zepbound? And my answer to them for a long time has been the better drug is the drug you can get. At different times in different markets, it has been one or the other of the two. The challenge around cost is a real one. One of the issues is that the way that weight loss medicines are covered by insurance is different than the way every other medication that you take is covered by insurance. Your benefits manager has to decide to opt in to what is called an anti-obesity medication rider. So, if your benefits administrator decides that they want to opt into that rider, you will likely have coverage for these medicines. If they’ve decided that they’re not going to opt into that rider, you will not have coverage for these medicines no matter what you do, unless you have type two diabetes.

So, it used to be back in the old days, like five years ago, that if somebody had pre-diabetes or signs of insulin resistance, some insurance companies would cover the diabetes medicine for patients who did not meet the criteria for diagnosing diabetes, but those days are over. If you have anti-obesity medication coverage, the coverage is typically quite generous. I have a lot of patients whose copays are in the neighborhood of $25 a month. The list price for these medicines is 11 to $1,300 a month. Obviously, that’s quite generous coverage. Both companies have pretty generous coupon offers that knock down the price by about 50%. Then you’re looking at something closer to 500 to $600 a month. Prohibitive for many people, no doubt, but better than $1,100 a month. The challenge is that I’ve had patients switch insurance, they get a new job and they go to their new job and their old job had coverage for anti-obesity medications and their new job doesn’t, and we’re left scrambling to think through how to manage that.

Emily Oster:

So, I have one more specific side effect question, which is actually from my father, which is is Ozempic face a real thing?

Dr. Gillian Goddard:

A lot of the side effects that people talk about with these drugs has to do with rapid and extreme weight loss and not with the medications themselves. Anyone who loses a lot of weight very quickly will lose weight in their face and gravity will take its course and they will have sagging skin. That is true not just on your face but on the rest of your body. Younger people tend to do better with this. Their skin is more elastic. Older people have less collagen and less elasticity, and so their skin can’t snap back as quickly. That would be true if they have lost 50 pounds through some other method as well.

The other one that people complain about a lot is hair loss. That is also just a side effect of rapid weight loss. It is evolutionary. There’s not a lot to do about it other than to make sure that you vitamin replete as you’re losing weight so that you can grow new hair back. But all of the side effects that people talk about specific to these medicines like Ozempic face and muscle loss are all things that would happen if you had the same degree of weight loss regardless of how you did it.

Emily Oster:

I want to talk about coming off the medications because one of the things we hear a lot in this discussion is this is forever. When you start going on this, you should expect to be on it forever. And that’s partly, I think, largely because when we look at the trial data, when people went off it, they regain a good share of the weight quite quickly. And you talked about getting people to their goal and then coming off it or people expecting to be on for a year or two years but not expecting to be on forever. You talk about how you think about the other side of this.

Dr. Gillian Goddard:

Yeah, absolutely. I think the first thing we should do is talk about that trial that said that everybody who came off of it regained the weight. That was a trial that was done by Novo Nordisk using Wegovy or semaglutide. They basically took the patients who had been in the trial for FDA approval, those patients were all on the highest dose of semaglutide, which is 2.4 milligrams weekly. And they randomized those people to either stay on 2.4 milligrams and continue to have diet and lifestyle support, or to stop the medication cold turkey and also got no diet and lifestyle support. It should not be surprising to anyone that the group that stayed on the medication maintained their weight loss and the group that stopped cold turkey with no support started to regain weight relatively quickly. I think it’s also fair to say that Novo Nordisk has a vested interest in having people take these medications on a long-term basis and not necessarily providing the research to discuss an off-ramp.

That has not been my experience. There are no studies that say this is the method you should use to take people off the medication. I have titrated people off and down on these medications. In a few cases, people were having such a good response to the medicine that we were like, oh, whoa, whoa, whoa, hold on. We got to go down quickly because you’re losing too much weight. But most people, it’s a really gentle downward titration, similar to the titration we do to put people on these medicines. The people who do the best coming off of them I find are the people who their lifestyle was not the issue to begin with. I mostly see women in my practice. I would say my practice is 90% women. So, these are mostly women often who have issues like polycystic ovarian syndrome where they have struggled with weight for their whole lives, their diets were dialed in and they were exercising, so they really didn’t make a lot of changes when they went on the medications.

They’ve achieved their goal weight as they’re titrating off the medication. They’re just continuing the same lifestyle that they already had when they started the medications to begin with. Those people tend to do really well. Some people prefer to stay on a small dose, and I have had patients who do things like stay on the smallest dose or they stay on the second-smallest dose, but they take it every 10 days or they take it every two weeks just to titrate themselves to stay in their goal range without taking the medicine on a weekly basis. But I’ve also had patients come off. I’ve had patients come off and be on no medication. I’ve had some patients come off and choose to be on a small dose of something like metformin, which can help with weight maintenance and decrease your risk of developing type two diabetes. Many of these patients are at risk of developing type two diabetes because of their biochemistry and their genetics. So, there’s lots of different ways to do this and I approach each patient differently.

Emily Oster:

More ParentData, including how to talk to your doctor about these drugs and how they relate to pregnancy and breastfeeding, including whether they boost your fertility, after the break.

Emily Oster:

So back to the New York Times wellness section. A response to how ubiquitous these drugs are is that we get a lot of panic headlines. And last week we saw a lot in the news right now about Ozempic being linked to vision loss. Will Ozempic make me go blind?

Dr. Gillian Goddard:

It is highly unlikely that Ozempic is going to make you go blind. What you’re referring to is there was a study published in JAMA Ophthalmology that was done by some ophthalmologists at Harvard. What they were looking at was an association between an extremely rare cause of blindness called non-arteritic anterior ischemic optic neuropathy and patients taking semaglutide. And now, they are a huge referral center for this particular type of optic neuropathy. And so they see a larger number of patients with this problem. But in fact it’s incredibly rare. It affects typically 2 to 10 people out of every 100,000 people. So it’s very, very rare. And what they found was in patients who had been prescribed semaglutide, both for diabetes and for weight loss, that there was an increase in the number of people who had this particular type of optic neuropathy. However, even when you increase something manyfold, if it is exceedingly rare like this is, it will still be exceedingly rare. So a four fold increase in an exceedingly rare disease is still a tiny, tiny, tiny number of people. And I have never seen this.

The authors also point out that what they showed was not a causal relationship. It was an association. And they themselves said that they didn’t know what a possible mechanism for this would be, that they couldn’t show that there was a dose relationship, and they couldn’t show that if patients stopped semaglutide, whether or not this would get better or not. And those are all key things, key components to showing that a relationship between a medication and a symptom are causal. You really cannot say that semaglutide causes this type of optic neuropathy, but rather there may be an association. Before we get excited about this at all, we need a lot more research into this. And it would not stop me from prescribing these medications to people. 

Also, remember not taking these medications or stopping them can lead to other much more common diseases like heart disease, high blood pressure, diabetes. Those diseases are super common and make people sick every single day. And so in my mind, the benefits of semaglutide still far outweigh the risks of this particular type of optic neuropathy.

Emily Oster:

I want to come to pregnancy and breastfeeding briefly because a lot of people ask about that, but it strikes me how important you are to this conversation and how valuable it is to have a provider who is thinking carefully about how can I take what we know from the science and work with the patients and think about their constraints and what’s going to work for them. So, other than just seeing you, which is not accessible to all people, I’m curious if there’s sort of one or two takeaways you would give people about either things to ask your provider or how to find someone to treat you that is going to work with you in the way that really is necessary to make this as effective as possible.

Dr. Gillian Goddard:

I think the biggest thing I would look for is I would look for someone who was treating patients who struggle with weight and treating patients with diabetes before this craze happened. Ozempic was approved in early 2018 and I started using it for weight loss the week it was approved. And I have other colleagues that I know who have a long history of experience in treating patients with diabetes and insulin resistance and they were using those medicines before all this happened too. I think there’s been a lot of getting on the bandwagon. And look, there’s a huge demand. I cannot blame anyone who has gotten into this in the last couple of years, but having a long experience with these medicines and feeling comfortable with titrating them would be the number one question I would ask about.

Emily Oster:

That’s great.

Dr. Gillian Goddard:

Unfortunately, those people are-

Emily Oster:

Rare.

Dr. Gillian Goddard:

… not always easy to come by, but that would be what I would look for.

Emily Oster:

All right. Let’s talk about pregnancy and breastfeeding. There are actually two interesting questions. Well, the questions I have about pregnancy and breastfeeding are a bit different. Most people accept the idea that we don’t recommend that you be on this during pregnancy, in part because during pregnancy you are trying to gain weight and grow another person, but we have found people who either are trying to get pregnant or who are on this and mistakenly get pregnant. That seems to be more common than we might expect. And I’m curious, how much should we know about how worry you should be if you were on this and then you got pregnant, and is there any truth to the idea that this is like a magic fertility drug?

Dr. Gillian Goddard:

As far as how worried you should be that you’re on the medication and you happen to get pregnant, I would say the evidence doesn’t really support that you should panic. These medicines are not going to get studied in pregnancy. A lot of the data that we’re going to get is going to be observational. There are some studies of exenatide, which was the very first GLP-1 in mice and giving exenatide to mice that are pregnant. There were some issues around low birth weight and that kind of thing, but they really found that it was all related to the mouse’s intake of nutrition. So, if you’re on this medicine and you get a positive pregnancy test and you’re four, six weeks pregnant and you stop the medication, I wouldn’t panic about that. I think probably things are going to be just fine. The size of the molecule suggests that it probably doesn’t actually cross the placenta so easily.

The issue is really around intake and I think especially most American women, we’re usually pretty well nourished going into pregnancy. We have some reserve that a couple of weeks is not going to have a huge impact on the health of a baby. The mice studies, obviously they had the mice on the drug through-

Emily Oster:

The whole time.

Dr. Gillian Goddard:

… the whole time not for a tiny fraction of the pregnancy. So, I definitely would not panic. There are a few case reports out there at this point of people who maybe didn’t know they were pregnant until late first trimester or early second trimester, and those case reports don’t show any significant issues.

Emily Oster:

All right. What about the fertility?

Dr. Gillian Goddard:

The fertility thing is probably real, and I think there’s probably two different factors at play here. The first thing is we know that insulin impacts ovarian function and how frequently people ovulate. Ovulation obviously being key to getting pregnant. If you don’t ovulate, you can’t get pregnant. When you improve people’s insulin sensitivity, they ovulate more regularly. And there’s maybe some data in women with polycystic ovarian syndrome that improved insulin sensitivity also improves egg quality. So, if you are improving insulin sensitivity, which is one of the things that these medications do and that weight loss can do sort of generally, then you may improve the frequency and regularity with which a woman ovulates and improve egg quality. If you’re doing both of those things, then you will improve somebody’s fertility. That’s one factor. The other factor is with tirzepatide specifically, so that’s Mounjaro and Zepbound. This has not necessarily been shown to be true of the other medications like Ozempic and Wegovy. But with tirzepatide specifically, they have shown that with certain low dose birth control pills, the way the medication affects how the birth control pill moves through your GI tract can delay its absorption. If that’s the case and you’re not super careful about taking your birth control pill regularly, you could have enough of a drop in the levels of the hormones in the birth control pill that would allow you to ovulate and then that would obviously allow you to get pregnant. The key there is really taking, and then you should do this all the time anyway but taking your birth control pill at the exact same time every single day. It may be helpful in this case to take it on an empty stomach, and if you’re really worried to use a different method of contraception.

Emily Oster:

Have many. There are many good methods at that.

Dr. Gillian Goddard:

We have so many.

Emily Oster:

What about breastfeeding? People have the baby, they want to lose weight. Is it okay?

Dr. Gillian Goddard:

We don’t have any data one way or the other. So, there’s not really much to hang your hat on here.

Emily Oster:

Is this a place you think we’ll get data? I think we absolutely will not in pregnancy. No one’s on purpose going to be giving this to pregnant women. Do you think we’ll get it in breastfeeding?

Dr. Gillian Goddard:

I think we probably will. I think that there’s a couple of things that are helpful to know. In animal studies, they did find exenatide, again, that was the oldest GLP-1. They did find exenatide in breast milk in animal studies. The thinking is that semaglutide, which is Ozempic, that the molecule is large enough that the amount that would get into breast milk would be relatively small. But the other thing I think is really important to remember is what I said about the oral absorption of these medications earlier. We only absorb a tiny fraction of what enters our GI tract. So, if you have a tiny amount of semaglutide in your breast milk and then your baby drinks your breast milk, then the baby gets semaglutide in their GI tract, but they’re only going to absorb up to 1% of it.

The exposure that the baby has to the drug is vanishingly small. And in fact, some of the databases that talk about the safety of medications and breastfeeding say that semaglutide is probably safe in breastfeeding for all of those reasons. If breastfeeding is really a goal of yours and is really important to you, the bigger issue is actually the impact that the change in nutrition and the change in hydration may have on breast milk supply. So, I do always warn people about that because some women’s bodies and breast milk supply will be more sensitive to changes in calorie intake than others. So, I don’t want somebody to be disappointed because they decided to go on one of these medicines and it tanked their supply. I’m more worried about that. I do think as babies get bigger and more resilient, it’s also a little easier to think about these things as well. Maybe you don’t want to go on semaglutide the week you come home from the hospital-

Emily Oster:

But if we’re asking, I’m still breastfeeding my 18-month-old one time at night, maybe this is not a major consideration for that.

Dr. Gillian Goddard:

Yeah, I think the amount of breastfeeding that’s going on, the age of the baby, all those things are factors in this conversation. Ultimately, I would argue we should give ourselves a little time and grace after we have a baby, before we start worrying about these things. But again, if it’s an 18-month-old comfort nursing at night and in the morning, that’s a very different conversation than someone who’s exclusively breastfeeding a four-week-old.

Emily Oster:

I always find it so much easier in some ways to answer these questions about breastfeeding than about pregnancy because you can say, look, we can look in the breast milk. With pregnancy, it’s the placenta, it’s this, how much is absorbing. It’s a very complicated system that we can’t get into. This is like, well, they’re consuming it, so we can just take it out and look at it and then we can answer.

Dr. Gillian Goddard:

One of the things that’s super interesting that they have done is they have done perfusion studies with GLP-1s and placenta where they have put GLP-1 in… This is obviously all experimental when the placenta is no longer in a creature’s body, but they’ve done studies where they perfuse the maternal side of the placenta with something that contains a GLP-1 and then tried to measure the GLP-1 on the fetal side of the placenta.

Emily Oster:

That’s cool.

Dr. Gillian Goddard:

A little bit gets across, but not very much. But when you’re thinking about systems in which to study these things, I think it’s interesting.

Emily Oster:

The placenta is a whole other podcast. The placenta is so interesting. It’s such an interesting organ.

Dr. Gillian Goddard:

It is. It’s also a gland. It’s a hormone gland. It makes all kinds of interesting hormones. So, from an endocrine perspective it’s fascinating.

Emily Oster:

Next podcast with Gillian will be details about the placenta. So, you prescribe a lot of these drugs, you think a lot about this. If you had to summarize the experience of the people that you treat with this, how would you describe it?

Dr. Gillian Goddard:

Life-changing, I’ve written thousands, probably tens of thousands of prescriptions for these medicines over the last 20 years. And that is probably the most commonly used phrase to describe how people feel about these medications.

Emily Oster:

Thank you so much. I feel like this was incredibly helpful in just understanding the landscape, so I really appreciate it. Thanks for being here.

Dr. Gillian Goddard:

No, it’s my pleasure.

ParentData is produced by Tamar Avishai, with support from the ParentData team and PRX. If you have thoughts on this episode, please join the conversation on my Instagram, @profemilyoster. And if you want to support the show, become a subscriber to the ParentData newsletter at parentdata.org, where I write weekly posts on everything to do with parents and data to help you make better, more informed parenting decisions. 

For example, Gillian has actually written out a lot of what she talked about today in an article titled, appropriately, “Ozempic, Mounjaro, Wegovy, Oh My! (yes, with the exclamation point), that dives even more into the numbers, and which you can read at parentdata.org.

There are a lot of ways you can help people find out about us. Leave a rating or a review on Apple Podcasts, text your friend about something you learned from this episode, debate your mother-in-law about the merits of something parents do now that is totally different from what she did, post a story to your Instagram debunking a panic headline of your own, just remember to mention the podcast too. Right, Penelope?

Penelope:

Right, Mom.

Emily Oster:

We’ll see you next time.

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