The Expanding Obesity Revolution: New Options

Mark Masselli (00:05)
The weight loss revolution is underway, kicked off by a new injectable drug. It's been shown to help patients
lose up to 15% of their weight, but it comes with a high out-of-pocket cost for most people. What else is on the
horizon for patients dealing with obesity? And how is the medical profession ensuring everyone can benefit?

Dr. Jamy Ard (00:24)
I Think we are at a watershed moment. This is really sort of an inflection point, if you will, in thinking about the
potential change in the landscape and how we conceptualize treatment of obesity.

Margaret Flinter (00:37)
Dr. Jamy Ard is co-director of the Weight Management Center at Wake Forest University School of Medicine.
He's at the forefront of research that's looking at how new obesity treatments can not only help patients lose
weight, but also control their type two diabetes.

Dr. Ard (00:53)
What we, you know, are seeing in, in the reason they tend to be so effective is that we're actually having a direct
impact on the pathways that control the hunger signals and the signals for satiation, how full you are after
consuming a certain portion of food.

Margaret (01:11)
And this is conversations on healthcare.

Mark (01:22)
Well, Dr. Ard, welcome to Conversations on Healthcare.

Dr. Ard (01:25)
Thank you for having me. I'm glad to be here.

Mark (01:28)
Yeah. You know, I wonder if we could just start with the, with the bigger picture. You know, obesity has such a
profound impact, I think since 1975, worldwide, it has tripled. certainly in America, 40% of all, all the
population are impacted by obesity. But if you were Hispanic, it is higher than that. And if you were a Black
American who is even higher than that. I wonder if you could just set the stage about the scope of this problem,
from your vantage point. And then we have so much other things to cover, but we thought we'd start there.

Dr. Ard (02:04)
Yeah. So you're correct in that the prevalence of obesity has definitely increased, and we've seen dramatic
increases, not only in the average body mass index, in the proportion of individuals who, meet the qualifications
for having a body mass index over 30, which is, technically defined as being, qualifying for obesity. we've also
seen, increases in the proportion of individuals who have the most severe levels of obesity, meaning they have a
body mass index greater than 40, and that category seems to be growing faster than lots of others. we're talking
mostly about adults in the, in that, statistic that you, referenced earlier. Mm-hmm. But the same, the same issue
as affecting children. And we are seeing this lifespan, sort of issue in terms of the impact of the, what we call the
obesogenic environment, having a fairly broad impact on, the entire population. But as you noted, some groups
of individuals seem to be more adversely affected by the obesogenic environment than others, and those
individuals tend to be, from groups that are historically disadvantaged or have more, challenges when it comes
to social determinants of health. Mm-hmm. And we, we think that part of that, disproportionate impact is related
to, you know, sort of a disproportionate exposure to the obesogenic environment, and that leads to, higher risk
of developing and sustaining a higher body weight.

Mark (03:46)
Well, you know, both Margaret and I want to first of all congratulate you on your election to the National
Academy of Medicine. And, and we wanna start off with the news that the oral drug from Pfizer, led to faster
weight loss than the weekly injections of Ozempic, which is an injectable we've heard so much about, in the
news. What, what's your take on this development?

Dr. Ard (04:13)
Well, I, I think it's a really interesting development in that, you've now, you know, we're on the pathway to
potentially add another option that's an oral option versus an injectable. I think having additional options for
patients is always a good thing. More of tools in a toolbox is always good. It leads to, healthy competition in the

marketplace. So hopefully prices will decrease as a result. I think it's also good for patients who don't like the
idea of giving themselves an injection. They might have a, an oral medication option, or people who might have
a series of adverse events or side effects with one type of medication might find that another one is more
suitable. So this is also, very good news.

Margaret (05:00)
Well, Dr. Ard, I really, appreciated going back a few moments. your comments on the social determinants of
health, the racial, and ethnic disparities and the obesogenic environment. And I, I hope our listeners were, were
catching all of that. sometimes I think that news is eclipsed, by the news on the, nightly broadcast on media, on,
television and other media about the pharmaceuticals. I think we hear three times as much sometimes about the
pharmaceuticals as the other factors. But I, I think there's been so much news and, and really I think confusion,
particularly about Wegovy and I'm, I'm wondering if you could, for our listeners, maybe just talk about the
profile, if there is one of the kind of patients that you think it's really indicated for and that you're prescribing it
for yourself.

Dr. Ard (05:51)
Yeah. I, I think these are really interesting points to make. so thanks for bringing this up. I, I think that the first
thing to say is in the healthcare space and in the space, especially where we are focused on treating obesity as
the, you know, sort of primary service that we provide for our patients, one of the things that we really want to
help underscore is that when we talk about obesity, we're talking about not just a number on the scale, but we're
also talking about, a negative health impact. So e excess weight that is leading to negative health consequences.
and that can range from a number of different things to, you know, from knee osteoarthritis and pain to back
pain or mechanical related issues to metabolic health related issues like type two diabetes or pre-diabetes or
hypertension. And so when we are treating patients, with these new types of agents, that is the target population
that we're really thinking about are individuals who are having negative health consequences of obesity. So
that's the first point. The second point I think, is that, when we look at these new agents, these, what we call
GLP1’s, that activate the receptors that, that allow for the body to produce more GLP1, what, what we, you
know, are seeing, and, and the reason they tend to be so effective is that we're actually having a direct impact on
the pathways that control the hunger signals and the signals for satiation how full you are after consuming a
certain portion of food. And it's really sort of hitting the reset button for a lot of people who will say, you know,
I haven't, I haven't had that sensation of fullness in some time. In, in the recognition of that is now much more
clear as a result of being, treated with these, this new agent or these new agents. And so that is a really important
distinguishing factor for people who say, yeah, I kind of don't have that signal to know when to stop eating.
Like, my, my signal to stop eating is a visual cue, or either the food is all gone. Those are the individuals who
we find to be really, responsive to this type of treatment. And when you combine that with the health concerns
and, and some of the specific issues that we also know that these types of drugs address, like, improving
glycemic control when we see people who have pre-diabetes or type two diabetes in addition to obesity, using
this type of medication really gives us a lot of bang for the buck in terms of the, you know, health effects that we
see, not only from the medication directly on say, blood glucose control, but also on the weight management
piece as well.

Mark (08:50)
You know, I may have some of this wrong, but just as I understand it Wegovy lacks a uniform set of
recommendations for when people should take it. And, and also that you're the incoming president of the
Obesity Society, also, leading an expert committee that's developing recommendations for when to start patients
on it. Can you give us a preview of what you're looking at and likely to recommend?

Dr. Ard (09:18)
Yeah. So what you're referring to Mark, is that we're going to be working on what we call a standards of care.
Mm-hmm. document and the standards of care really are going to be designed to help clinicians, both in the
primary care space as well as providers in the specialty space of obesity management, to really understand what
do we think of as standard practice across the board, and what are the evidence, what's the evidence that we
have that helps to support that. and some of that may be in the form of clinical trials. Some of that may be real
world evidence, some of that may be expert opinion, but we want to give clinicians a way to inform their
thinking and decision making such that by the time that they are at the point of care with the patient, they have a
sense of nine outta 10 clinicians would land in this spot given this situation. So we won't necessarily, come out
and say, you know, follow this pathway, this algorithm and Wegovy as indicated in, in all of these situations.
Mm-hmm. But what we will want to do is inform the clinician so that they can be, evidence based and
scientifically grounded in their decision making at the point of care. So the patient can understand, this is what
acceptable care looks like for obesity treatment. So for example, we know that obesity is the chronic disease and

requires chronic treatment. And if a, a, a patient is seeking care and they hear a provider or professional say,
well, we're going to only think about doing this treatment for a few months and then stop, then that's a red flag.
And the patient should know this is not the standard of care, long-term treatment, chronic therapy that may
require, you know, changing or evolving that therapy over time. But that's what the, that's the type of approaches
that we will want to inform, for the, the provider.

Margaret (11:19)
Well, Dr. Ard, a couple of, moments ago, I think you just did a great job of clarifying for our audience, that's not
clinical. some, some are and some aren't, why these drugs work? This, this idea of, people recognizing satiation
or just when they're full, as we would say. but when it comes to, selecting different drugs, the Ozempic, and,
Wegovy, maybe you could just elaborate just a little bit for our listeners. how are they different and what are the
side effects of each one? Do they different in their side effect profile?

Dr. Ard (11:53)
So, fundamentally, Margaret, both of these drugs are the same thing. Okay. So they are both, if we use the
generic term for both of the drugs, it's semaglutide, that's the molecule, the name of the molecule. And the only
difference between Ozempic and Wegovy is that Ozempic is indicated for, or branded for use in type two
diabetes. Mm-hmm. Its indication is for type two diabetes and the dose of Ozempic, the maximum dose that it
goes up to as 2.0 milligrams, for Wegovy, same drug, but just branded for use in obesity treatment. Great. And it
goes up to 2.4 milligrams as the maximum dose. so otherwise, same side effect profile, most people will
experience some type of GI related side effect, generally mild in nature, that tends to decline over time with
continued use of the drug. and that GI side effect tends to be mostly nausea, but some people have diarrhea or
constipation. excuse me. And then, generally speaking, as I said, as you slowly titrate the dose of the drug,
people will tend to have, in, in experience longer use of the drug. They tend to have fewer of those side effects.
but you will see the same reported side effects for Ozempic as you do for Wegovy.

Margaret (13:21)
Well, thank you so much for clarifying that. I think that point about the indication, really being the difference is
very helpful for people. Thanks.

Mark (13:28)
Now, all of those side effects really, are derived from clinical trials. and that Ozempic, as I understand it, trial
only lasted two years. I'm wondering if you think that's long enough, and I, I'm not sure about Wegovy, so
maybe you can, give us the information on, on both of those. But, in the past, other drugs to treat obesity have
been pulled because of adverse health effects. And I guess just trying to figure out, what, what, what's the right
length, particularly for such important drugs that ha are going to have wide impact, because of, the scope of the
problem?

Dr. Ard (14:10)
Yeah, you're right. I, I think in the past, one of the things that, has caused all of us to have a little bit of P T S D
is that, you know, we go all in on these new medications and we feel really excited about the potential impact.
And then, over time we identify some problem that's crept up, that with time and more, experience and
exposure, we start to see a signal that suggests a safety concern. so one of the things I think that makes us feel a
little bit more optimistic here in this case and different is that, these types of medications, GLP1 medications
have been around in the diabetes space for actually quite some time. And so even though we might have clinical
trials that go out to a two year timeframe, we've actually had post-market experience. So after the drug has been
approved in, in use, for over five to 10 years now. Mm-hmm. And so we see that these molecules with
prolonged use, look to certainly be safe and even safe lives, in the space of diabetes treatment. And so there's
ongoing clinical trials now related to cardiovascular outcomes that, are for obesity in particular, that we
anticipate, positive results. And if that happens and we see that treatment at the higher dose, of the Wegovy in
individuals with, known risk factors for heart disease or heart disease, actually reduces the risk of, some type of
cardiovascular event, then that really is a, a game changer when it comes to thinking about the safety of the
drug. Mm-hmm. That's very helpful. Thank you. I wonder, if I can, veer a little bit off of the, the drug itself and
into what you're seeing in your patient population as people who are obese experienced significant weight loss.
are you seeing, impact on people's social mental wellbeing, activity level ability to engage in activities they
couldn't before? You know, beyond the medical, are you seeing a change in, in impact on life and lifestyle for
folks? Yeah, we're, we're seeing lots of, important changes in quality of life for our patients. And I think this is
one of the things that's really important and often underestimated in terms of impact that treatment of obesity
has for, for our patient population. a lot of people are dealing with, often in a very silent way, a lot of the
negative consequences of excess weight gain. And that ranges from poor self-esteem and challenges with

confidence to, pain and inability to do the things that they want to do, that make life fulfilling. And so we hear
stories all the time about people who are able to comfortably take a, a trip, in a, in an airplane, for the first time
in some time, or they've been able to have their nice vacation with the family and not sit on the sideline while
everyone else is on the rollercoaster. or just being able to do daily, you know, life activities that we all take for
granted, like being able to, you know, wash your own clothes and clean your own home, or take care of a
another family member. those are the things that I think oftentimes when we live without obesity, we just take
for granted. And people who have lived with obesity, value, the recovery of those, abilities for sure.

Mark (17:53)
You know, that's such an, sensitive, insight into the struggles that people have. And I've, I've heard you talk
about the sort of, the old approach of sort of a moral approach of, you know, ‘Hey, get up and move,’ and not
really understanding the larger set of consequences that, or, or issues that people face, who are dealing with
obesity. And I guess I wanna sort of pull that thread and say, you know, there are roughly 110 million
Americans eligible for anti-obesity medication, but given all the value that you just said, we've got Medicare, I
believe, legally prohibited from paying for it, and also both on 60 minutes. And I think Wall Street Journal, both
have reported that private insurers aren't covering it as well. So I'm wondering if you can just help us connect
the dots of its benefits and also the, issues of, coverage because it, it does seem to, greatly improve, the lives for
many people in those, ways that you, just, illuminated.

Dr. Ard (19:03)
Yeah. So I, I think we're at a watershed moment. This is really sort of an inflection point, if you will, in thinking
about the potential change in the landscape and how we conceptualize treatment of obesity. for the longest, a lot
of the, the basic thinking about how we treat obesity was rooted in the idea that, well, it's just a calorie
imbalance and people are typically eating too much and exercising too little. And obviously if we reverse that,
then that will solve the problem. and as we know that that clearly has not worked, and it doesn't absolve us from,
continuing to focus on how we prevent excess weight gain and, and modify our environments in a way that
make healthy living more, easily attainable for a larger portion of people. But for those of us who have, you
know, developed obesity and, and live with obesity, the, that mantra and that that idea of eat less, move more
just doesn't work. And we have to have a biological process that actually helps to deal with the core issue. And
so this is at the, you know, at its core, an issue at the brain level where the brain is not responding to this
environment appropriately in terms of helping us to manage the, you know, energy dysregulation that has
happened in this environment. So medications actually really do get at that core issue, and they help the
individual, better respond to this environment and reduce intake in a way that, allows for that individual to, to
lose weight. And as our understanding has changed and evolved over time, we think that, yeah, our policies and
the way we identify treatment and, and take care of patients, shouldn't evolve with that. and so this, this is why
these types of conversations are so important, because it helps us to highlight where our bias thinking in the past
continues to have an impact on policy and influences decision making around resource allocation currently. And
we can change that, that is totally within our power to change that. And we know that if we can continue to have
these conversations and expose people to this new information, then hopefully we will start to change hearts and
minds and get people who are in the positions to make these decisions to understand the impact that, the disease
has and that, you know, we don't treat any other chronic disease in this way, and this, treatment should be on par
with high blood pressure or heart disease, or, any type of cancer that we treat.

Mark (21:50)
Are you familiar with any cost benefit studies that are underway now that would, help inform, policy makers?

Dr. Ard (21:59)
Yeah, so they're, they're actually a range of, of cost benefit studies that, have been published in analyses that
have been done. And, you know, one of the things that I think a lot of people are concerned about right now is
that, as you mentioned before, the cost of GLP1s, the newer agents like Wegovy are definitely really high, right?
These, these are drugs that are costing over a thousand dollars a month if you had to pay out of pocket and
someone's bearing that cost. And so, you know, payers, insurance companies, employers, who are self-insured,
they're definitely very hesitant to say, well, we're gonna open up the pocketbook to, provide full coverage of that
for everyone mm-hmm. Who might be potentially eligible. And that's a scary number that comes up. Mm-hmm.
But the, the point that I would like to make is that not everyone needs that, that level of treatment. That's number
one. Number two, we have plenty of other good options that have, we've used successfully, you know, to this
point and will continue to use, that are definitely accessible for a lot of patients. It's just that these newer agents
seem to be, a bit more potent for a larger group of people. And I think that when we think about how to do
obesity treatment smartly, we can define ways and provide, support for people to actually put together treatment
plans that are cost effective. And we will continue to do research in terms of real-world evidence and be able to

identify in large populations of people who is, is actually going to see the cost savings as a result of treatment.
Mm-hmm. Because, it's not everyone exactly. That might be, someone who's gonna see cost savings in the short
term, especially if you are otherwise relatively healthy, but you might have excess weight and benefit from that,
say, in, in relation to quality of life. Okay.

Margaret (24:00)
Well, certainly, Dr. Ard, another area of health policy and coverage has been changing rapidly. Perhaps the
enduring, legacy of the Covid pandemic is telehealth. and also with it, the increased, availability and the
coverage of remote patient monitoring as kind of an integral part of, caring PA for patients with chronic
challenges. And I understand your practice, is using remote monitoring, to help provide some lifestyle therapy
or interventions for those who are severely obese. Tell us, how is this working? is it an adjunct, to the medical
treatment and, and what's your thoughts on the promise of, remote monitoring for patients?

Dr. Ard (24:41)
Yeah, so remote patient monitoring is really central to everything that we do in our center. and the reason it's so
important is it's really, it gives us a bird's eye view, if you will, of what's happening within the patients, day-to-
day journey, as they are, you know, trying to get healthy, lose weight, improve lifestyle, make changes, in the
course of their treatment plan. It also enables us to be able to provide telehealth, with confidence about what the
outcome is, right? So rather than having to re rely on self-report or an occasional weight, here or there, or an
occasional blood pressure, we actually have the data in front of us and can see that, on a regular basis. And it
allows us, for us to be able to synthesize that information, at a population level and be able to say, of all the
patients that we have within our cohort, this is how many are losing weight? This is how many people are
weight stable, this is how many people have gained weight? Do we need to do something in that group of people
who are mm-hmm. Gaining weight, not responding to treatment. so it just really enables us to be able to provide
a different level of care, even though the patient is not coming into the office.

Mark (26:00)
Well, that's great. You know, Dr. Ard, Margaret mentioned earlier your impressive work, focusing on social
determinants of health and health inequities research, which tells us that black patients already receive less
obesity treatment than white patients, despite facing those higher prevalence that we talked about at the top of
the show. what can the entire health system and sector do to address these disparities? I know in our practice,
we're, we're a participant in the All of Us research program really focus in on making sure that the whole
rainbow of, of American, residents are, are involved in these clinical trials. But, tell us some more.

Dr. Ard (26:41)
Yeah, so Mark, I think that's a really important point is first thinking about as new treatments and therapies are
developed, who are the patients and the participants in those trials? And when we have trials that don't have
representative populations, especially for disease states that adversely affect one group or another, then it makes
it hard for us to generalize those treatments into other populations. So I think that's a very important point. And
to that, I think one of the things that helps improve representation within the trials is, having representation
within the investigator teams, right? So thinking about who are the study sites that are participating? If that
population of investigators looks one way, then it's likely that the population of patients will also look a
particular way. And, you know, I think we can do more to encourage and support a broader, engagement in
clinical trials and participation, both from investigators of diverse backgrounds as well as patients. And then the
last thing I think I will say is I think it's important for all healthcare providers, anyone in the healthcare system
to understand the impact of these social determinants of health and realize that, a lot of healthcare does not
happen within the confines of an office visit. and what we are doing is really a very small drop in that bucket. So
if you don't really understand those social determinants of health and you don't have visibility into what your
patient is dealing with when they leave the encounter, then I think that's an area of opportunity for us. And mm-
hmm. It can shed some light on understanding the feasibility even of the treatment plan that we've put together.
I've had lots of patients who leave the office and come back and say, you know, look, I tried, but there were all
of these challenges that made implementing this plan totally impossible. And that's something that we have to
think about more critically. Yeah.

Margaret (28:49)
Well, Dr. Ard, while we've got you with us, I'd like your, thoughts on, on just one more thing before we close.
if, you know, over the, the, arc of time, different measures in practice, sometimes get challenged as to how valid
they are, and that seems to be going on right now with, BMI or Body Mass Index. many, in the field have
expressed doubts about the effectiveness or the usefulness of B M I for people of all races and ethnicities, and

some critics, who believe that B M I, as a measure adversely affects Americans of color, maybe by shaping the
diagnoses and treatments they receive. We'd love to give you a chance to comment on that before we close.

Dr. Ard (29:30)
Yeah, sure. So I think that body mass index is definitely useful. In some ways it's an epidemiologic tool. It
actually helps us with all the stats that Mark led off the, conversation within terms of understanding the size of
our population and, and on average and, and what that looks like. but it, it is not a diagnostic tool in and of itself.
So as I talked about before, obesity is a combination of looking at excess body weight, excess fat, and health
consequences related to that. And so you can't get that simply from the number. You can have two people in
front of you that have a very different B M I and they got there in very different trajectories. One could go from
A B M I of 40 to 35, the other could go from 30 to 35, and they would have very different health profiles as a
result of the trajectory of the weight change. So when we look at BMI clinically, it is a screening tool that
actually is part of a, additional number of variables that help us to put together a whole picture of the patient. I
think the idea that B m I is biased in some way or another, I think is there's a lot more nuance to that, that
conversation. Mm-hmm. And then, and my take on that is that I think, if we were to play out the idea that B m I
were significantly biased in one way or another, there might be unintended consequences in terms of
underdiagnosis lack of engagement, even more so than what we already know mm-hmm. In terms of engaging
African American populations, for example, around the treatment of, of obesity and helping people understand
the health consequences that might be, in the future for them. So I think short story is, B M I is not exactly
perfect, but it's not meant to be a diagnostic tool. Mm-hmm. It's a screening tool, and we need more research to
define, a better marker of what we actually mean when we say energy imbalance in the things that lead to
obesity and excess weight gain.

Mark (31:42)
Well, Dr. Ard, thank you so much for joining us today for your commitment to this area, to the research and
scholarship that you bring to your work. thanks to our audience, there's more online about conversations on
healthcare, including a way to sign up for email updates. Our address is chcradio.com. Thank you again, Dr.
Ard.

Dr. Ard (32:01)
Thank you. Thank you for having me.

Margaret (32:08)
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