(cheerful music) - [Kelly] Much attention
has been paid recently in both scientific
circles and in the media to a drug for weight loss
newly approved by the FDA. A flurry of articles in
the media hailed this drug as a breakthrough. This was prompted by the
publication of a landmark article in the "New England Journal of Medicine", addressing the impact of this medication in a large clinical trial. Today's guest is one of
the authors of that paper. Another flurry of media attention occurred as the drug became available, with news that supply
couldn't keep up with demand. Welcome to "The Leading Voices
in Food" podcast series. I'm Kelly Brownell, Director
of the World Food Policy Center at Duke University. I'm pleased to be joined
today by Dr. Thomas Wadden. He's the Albert J. Stunkard Professor and former Director of the Center for Weight and Eating Disorders at the University of
Pennsylvania School of Medicine. He is one of the most
highly regarded experts on treatments for obesity, having done some of the
most important research on very low calorie diets, a variety of medications,
bariatric surgery, intervention in primary
care settings, and more. Tom, welcome. It's so
nice to have you with us. - [Tom] Oh, it's a pleasure
to be with you, Kelly. - [Kelly] You and I grew up
together in this profession, having spent some early years together working on treatments for obesity, and you're one of the people
in the field I admire most, both for the quality of your work and also the breadth of your knowledge across a variety of
treatments for obesity. So let me begin asking something regarding our former
mentor, Albert Stunkard. So one of the most famous
quotes of all time in our field came from Mickey Stunkard
in 1959 no less, way before the field was really paying
attention to obesity, and he wrote this, that "most obese persons
will not stay in treatment. Most will not lose weight. And of those who do lose
weight most will regain it." There was a stark honesty to this and it motivated Stunkard
to help overweight people. So if we fast forward to today, do you think this is
essentially still true? - [Tom] Well first, let me just say that Dr. Stunkard's statement
sounds somewhat critical or today we might say stigmatizing
of people with obesity. You know, they won't stay in treatment, they won't lose weight, they'll regain it. And Stunkard as you know
perhaps better than anybody, was an extremely
compassionate, empathic person and he knew that the
limitations to success were with the treatments available and not with the people who had obesity, just to clarify that. To answer your question, the first two parts of
Stunkard's statement that people won't stay in treatment and people won't lose weight were probably no longer true
by the early to mid-1980s. And pioneers like yourself showed that if you gave
people a structured program of diet and physical activity, and most importantly if you
gave them behavioral strategies to improve their treatment adherence, then 80% of people would stay in treatment for 16 to 26 weeks and they'd lose an average
of 6% to 10% of their weight. So what remained however,
and remains today, was that people have trouble
maintaining the weight loss. And that's something that
we're still challenged by. - [Kelly] Well, it's nice to start off on that optimistic note with hope that people
will go into treatment. Let's talk about the drug. So what is the new drug
and how does it work? - [Tom] Well, the new
drug is called semaglutide and it comes in a dose of 2.4 milligrams and it's injected
subcutaneously once per week. The drug at the retail
level is known as Wegovy. Some people will know about semaglutide for the management of type 2 diabetes. It is used at a dose of 1.0 milligrams and it's called Ozempic. So Ozempic was approved
first many years ago. Now, semaglutide is a glucagon-like peptide
1 receptor agonist, and that's a mouthful. But glucagon-like peptide
1, GLP-1 for short, is a naturally occurring hormone that is released by the body when food, particularly carbohydrate,
hits the stomach and GPL-1 is released by
cells in the small intestine and it does several important things. First it signals the
pancreas to release insulin to pick up the glucose that's coming in. And then it also slows gastric emptying, which as you know, leads to greater feelings of fullness. And then finally, these
GLP-1 receptor agonists are hitting a part of the hypothalamus that stimulates fullness or what's known as satiation receptors, so people feel full
earlier when they're eating and don't eat as much food. I think you may remember, Kelly, that naturally occurring
GLP-1 has a very short life when it's released. It's active for about
two to three minutes, so you have a short feeling of fullness. But these new drugs,
semaglutide 2.4 milligrams has a half-life of seven days. So people are feeling greater fullness and less hunger sort of around the clock, and as a result, they
are just eating less. And to use your terms, they are less responsive to all the cues in the toxic food
environment that are saying come on, it's time to eat more, it's time to have a large
serving of ice cream or sugar-sweetened
beverages, whatever it is, people don't seem to be as vulnerable to the toxic food environment. - [Kelly] I really appreciate the fact that you've taken a
pretty complex subject, namely the physiology of this
drug, and made it come alive in terms that most of us can understand. So thanks for that. So before you talk about the weight losses that the drug produces, you mentioned before that some treatments are producing weight losses,
5%, 6% of body weight. Can you place that in context for us? I mean, is that enough to
produce medical benefit? Are the people losing weight happy with that degree of weight loss? - [Tom] Sure, most individuals who go through a behavioral
treatment program will lose about 7% to 8%
of their weight on average. And those weight losses are associated with significant improvements in health. The landmark study in this area is the Diabetes Prevention Program published in 2002 where
people with pre-diabetes lost seven kilograms,
about 7% of their weight and they exercised 150 minutes per week. And those individuals with pre-diabetes reduced their risk of developing
diabetes over 2.8 years by 58% compared to the control group. So that's a really important finding that modest weight loss,
modest physical activity prevents the development
of type 2 diabetes. And weight loss is also going
to improve blood pressure, it can improve sleep apnea, so modest weight losses have benefit. But two things. First, larger weight losses have greater improvements on health. That's important to know. It's in a linear relationship there. The more you lose usually the better the
health improvements. And two, most people who
are seeking to lose weight want to lose about 20%
of their body weight. So if you're a 200-pound female, a 250-pound male, you want to lose 40 to
50 pounds respectively. And so larger weight
losses are highly desired. - [Kelly] So how do you deal
with that psychologically when somebody's goal is so far beyond what treatment typically produces? I mean, can people come around to the fact that the smaller weight
losses are really good for me and I've accomplished a lot even though I may not get to my goal? - [Tom] Well, I always tell people, I know you want to lose 40 pounds. Let's start with the first 15 to 20. Let's focus on that 'cause you have to go through 15 to 20 to get to 40, and let's see how you feel after you've lost the initial weight. And I can't promise
you you're going to get to 40 pounds for potentially
genetic or biological reasons, but let's try to achieve
what we can achieve then we can focus on larger weight loss. And many people are more
satisfied than they'd imagined with a more modest or
moderate weight loss, even though the dream is
to lose more than that. - [Kelly] Okay, so back to the drug then. This big clinical trial
you were involved with that was published in the "New
England Journal of Medicine", can you quickly explain the trial and then tell us what you found? - [Tom] There were four
big clinical trials of this medication that were presented to FDA for approval, but the seminal paper published
in "New England Journal" treated about 1,961 participants. And everybody got lifestyle modification on a monthly basis with a dietician for 15 to 20 minute visits. And then on top of that, half the participants got assigned to semaglutide 2.4 milligrams, the other half got placebo. And they were followed
for a period of 16 months. And the reason it's a 16-month trial is because you have to
introduce the drug slowly over a four-month period in order to control
gastrointestinal side effects. So as you start to take this drug, you're likely to experience
a little bit of nausea. About 45% to 50% of people do so. So some patients, about 20%, will experience vomiting. Constipation and diarrhea also occur in response to the drug. So if you slowly introduce the drug, you can prevent some of those symptoms. And so it's not till four months that you're on the full dose of the drug and that's why they run
the trial for 16 months so people have an opportunity,
been on drug for one year. And so what happens at the
end of this 16-month period is that the participants who get lifestyle light with placebo, lose 2 1/2 percent of their weight. That's about what we'd expect. Those who get semaglutide, lose 15% of their body weight. So a remarkably robust weight loss. And when you break it
down a little bit further, what happens is that 69% of
the people on semaglutide are losing 10% or more of their weight. And then 50% are losing 15%
or more of their weight. So that's a substantial loss. And this is something that I'd never seen in this kind of a trial. One third have lost 20%
of their body weight. And those weight losses are cumulative. So the 69% who lost 10% of their weight, that includes the people who lost the 15% and 20% of their weight. But as you well know, those are substantial losses
where the average loss is 15% and that's achieved by 50% of the people. That is double what we get with our best behavioral treatment and it's about double what you get with most weight loss drugs. - [Kelly] Yeah, that's
pretty darn impressive to double the impact. I mean, most people'll be excited with a a little bit of improvement. That's a lot of improvement. So certainly we have to
take note based on that. You know, when you talked
about the side effects, you were talking about the, I think, fairly immediate side effects
of beginning to take the drug, and then it takes four months for people to get up to the full dose. Are there side effects that exist beyond that four-month period? - [Tom] Well, most people will be through those
gastrointestinal side effects within the four-month period. But in fact, if you go out to 16 months, there will be a small percentage of people who have nausea, diarrhea, et
cetera, throughout the trial. And you just try to help those people with their side effects by doing things like chewing their food more thoroughly, eating smaller meals but more of them, drinking more water. All of that can help
them control their nausea if it's persistent. I think that the most
serious side effect, Kelly, is that about 4% of people are
going to develop gallstones or need to have a gallbladder removed and that is just a consequence
of the large weight loss. Anytime you have large weight loss, whether it's from a very low calorie diet, from bariatric surgery, or from these medications, you're going to find that a
small percentage of people do have gallstones and
will need attention. - [Kelly] And what about the fact that people need to get this by injection? Are people able to do that okay or is that a deterrent for
people using it on a broad scale? - [Tom] It's a very good question. I can tell you that I have injected myself on several occasions just
to see what it's like and most cases just find
a fat fold in the stomach and inject yourself. The needle is so small
that you can't feel it. So once people try it, there's
really very little hesitancy. I think certainly some people would think, "I don't want to be injecting
myself with this thing", and they may not even come
in, but once you try it there's not a problem. And right now there is an
oral version of Ozempic. It's called Rybelsus. So it's the same medication
for type 2 diabetes but in oral form rather
than sub-q injection. And a trial is currently underway to see if we can make an oral version of semaglutide injectable drug and I think that's going
to prove to be acceptable. So that barrier should
be eliminated over time. - [Kelly] So what happens if
people stop taking the drug? - [Tom] I think you know the answer. People stop taking the
medication are vulnerable to regaining their weight. And some people would say, well, that illustrates
the drugs a failure, because you just take
it and you lose weight and you regain it and
you're no better off. But I am on a medication
for high blood pressure and on a medication for high cholesterol and I can assure you if I
stop taking those medications, my cholesterol and blood
pressure would go up. So this speaks to a very important issue which we have to look at obesity in probably a majority of persons as being a chronic health condition for which they're going to
need long-term ongoing care and you would need to take
these medications indefinitely just like I take my hypertensive or cholesterol
medication indefinitely. - [Kelly] You know, the
description of the cholesterol and blood pressure drugs
is a great example. And I think this really speaks to the issue obesity stigma, doesn't it? Because if you have these blood pressure, cholesterol drugs, and lots of others, if people are taking them
and they're effective and then they stop taking them and then the medical condition comes back, it's even more evidence that a drug works. But in the case of some
of these obesity drugs, people say, well if you stop taking it and you regain the weight, it's
proof the drug doesn't work. So how do you think that might be bound up with kind of general social attitudes about people with obesity? - [Tom] It's such an important point. So persons with obesity
are still stigmatized as you, Rebecca Puhl, and
so many people have shown. And there's just so much
unrelenting stigmatization of people saying, you
know you should be able to control your weight by exercising more, cutting down on what you eat, push back from the table. You know, it's your
problem, your shortcomings in self-control. So people with obesity are stigmatized. Similarly obesity
medications are stigmatized. Anytime I give a talk to physicians, I'll ask how many would consider prescribing an obesity medication? And only about 10% of hands go up at most. Then I'll ask, well would
you prescribe a drug for hypertension or cholesterol? Everybody's hand goes up and I say, well what's
the difference here? And people invariably say, well, people should be able
to control their eating and exercise with their willpower. And I say, well, it's an
illness, it's a disease in part caused by this
toxic food environment so why are you treating that differently? You allow diabetes medications. That's caused by eating
behavior to some extent. So I think you're correct. There's this profound stigmatization
of people with obesity and of the medications. And I think that view
is beginning to change. One of the most important things about this new medication semaglutide, and there'll be a new drug from Eli Lilly called tirzepatide, is that doctors, endocrinologists and primary care physicians, are comfortable with these
glucagon-like receptors because these are diabetes
drugs that they prescribe and they're willing to
prescribe those long-term. Now they may be willing to
recognize obesity disease which requires long-term treatment and they feel comfortable with the drug that it's not going to
have adverse side effects. So I hope this is a turning
point in the stigmatization of persons with obesity
and of obesity drugs. - [Kelly] Tom, how much does the drug cost and is it covered by insurance? And what about people on
Medicare and Medicaid? - [Tom] This medication, if
you just go to your pharmacy and ask for it, I think
is currently priced at about $1,300 per month. And so that is a very high barrier to the vast majority of people who would want to take this drug. It's possible and I hope that the price is going to come down, but I haven't seen any indication of that. The medication is covered by some insurers and some employers, so some people will
have the benefit of it. But I think as you know,
Medicare and Medicaid do not cover any obesity
medications at this time. There's a very important piece
of legislation in the Senate and in the House called the
Treat and Reduce Obesity Act and part of that bill is to get Medicare to cover obesity medication. Even though they've got a
terrific new medication, most people who would benefit from it, and particularly people of color who have higher rates of
obesity, minority members, will have a very difficult
time getting this drug to use it appropriately. - [Kelly] So you mentioned that Eli Lilly may be coming out soon
with a competitor drug. You think the competition
will reduce the cost? - [Tom] I would hope it
would reduce the cost, but I can't say that I
have any advanced knowledge of that or any assurance
that that's going to happen. Eli Lilly has put a lot of
money into the production of their medication. Their medication tirzepatide looks like it will be certainly
as effective as semaglutide if not more effective by two
or three percentage points. So I think probably the best bet for having a reduction in cost is that another medication very similar in its mechanisms of
action to semaglutide, it's called liraglutide 3.0 for obesity. It is a GLP-1 receptor agonist, it's just not as effective, it produces an 8% weight loss, it's going off patent I
believe in 2023 or '24 and when it goes off patent, I think that there will be generics to at least make that drug available at a very reasonable cost. That drug currently, I believe, is at about $600 to $700 per month, but it should come down dramatically when it goes off patent
and there are generics. - [Kelly] And for people
who have health insurance, are insurers covering the drug? - [Tom] A smattering of
people are covering the drug at this point. I don't think there's universal coverage. If you're under Blue Cross Blue Shield or whatever your company may be, remarkably the University of Pennsylvania is covering some of these medications which I'm delighted to see. But you would have to check
your insurance plan carefully. There are for people who do have coverage, there are coupons to get your costs down to as little as $25 a week. So it's really worth looking into. And I know that Novo Nordisk, which manufactures semaglutide, is trying to work with insurers to get more to pick up
the coverage of the drug. Let's hope that they reach some insight that'd be important to
reduce the cost of this drug to make it more available to
people who really need it. - [Kelly] Let me ask
a big picture question to end our conversation. So where does this drug fit in the broad scheme of various options for treatments for obesity and how would someone or their physician know if this medication would
be a good option to pursue? - [Tom] Sure, if we follow
just the FDA guidance and the guidance of expert panels, this drug is appropriate for people who have a body mass index of 30. So you can go and your doctor
will measure your weight and calculate your height,
and tell you what your BMI is. So at a BMI of 30, you're
eligible for this drug if you've tried diet and exercise, which just about everybody will have, and you haven't been
successful with that alone. I think that the drug is most appropriate for people with a body
mass index of 30 or greater who have significant health complications, meaning they have type 2 diabetes or they have hypertension
or they have sleep apnea. If the drug's going to
be limited availability 'cause it's cost, I would
try to get it to the people who have the most to benefit in terms of improving their health. That's the primary reason to
seek weight reduction I think. To address your question, technically the drug's available to people with a body mass index of 27 who have a comorbid condition
such as hypertension or type 2 diabetes. And if you've got a BMI of 30, you would like to get this drug to people who have the highest BMIs and have the greatest benefit to health. Those individuals with higher BMIs at 35 who have a comorbid condition, they're eligible for bariatric surgery which is the most effective
treatment for obesity. If you look at the most
popular surgical treatment right now, it's called sleeve gastrectomy, where you simply remove 75% of the stomach so you can't eat as much food and it does have improvements
in appetite related hormones such as ghrelin, the hunger hormone. That is dramatically
suppressed by the operation so people are less hungry,
have less desire to eat. And so that operation
produces about a 25% reduction in body weight at one year. And at three to five years,
people still have 20% off. So a person who's got a BMI of 35 or more with a comorbid condition
such as type 2 diabetes wants to talk with his or her physician and see if they might benefit
from bariatric surgery. If doctor and patient don't
think that's the option, you would like to consider
an obesity medication to help you just control
your feelings of appetite, hunger, and satiation, to make it easier to eat a lower calorie diet, to make it easier to want to get out there in physical activity. So that is the big picture of the options. Diet and physical activity for people who have overweight and obesity
without health conditions. And then you add medications for people at a BMI of 27, 30, or greater who have health complications. And then you add bariatric surgery when medications don't work. - [Kelly] Well, Tom, it's nice that there are more options
available to people with obesity and also to physicians who
are providing the treatment. And boy, if you think back
to, you know, the early days when we got started in our career, there weren't that many options. And the fact that the there's
more attention to the problem, more funding for studies,
and ultimately more options is a really good thing. So thanks so much for
sharing this picture with us. We really appreciate it. - [Tom] Thanks so much.
Pleasure to be with you. - [Kelly] I agree.
(bright music) So today's guest has
been Dr. Thomas Wadden of the University of Pennsylvania. And thank you for listening. If you'd like to subscribe to "The Leading Voices
in Food" podcast series, you can find in on Apple Podcast, Google Podcast, or your
favorite podcast app. Podcasts and transcripts
are also available on the website at the Duke
World Food Policy Center. This is Kelly Brownell.
