Leading Pediatric Obesity Research with Justin Ryder, PhD

Episode Transcript
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Erin Spain, MS (00:10):
This is Breakthroughs, a podcast from Northwestern University
Feinberg School of Medicine.
I'm Erin Spain, host of the show.
The landscape of pediatric obesitytreatment is evolving, and Northwestern
Medicine scientists are at the forefrontof this research into the most effective
ways of treating obesity in children andteens and improving their access to care.

(00:34):
My guest today, Dr.
Justin Ryder, is a clinical andtranslational obesity scientist,
working on several NIH funded projectsfocused on understanding how pediatric
obesity impacts chronic disease riskand how biology drives weight regain.
He's an associate professor of surgeryand of pediatrics at Feinberg and
serves as the vice chair of researchfor the Department of Surgery

(00:57):
at Lurie Children's Hospital.
He joins me today to talk about hisrecent work, which includes studies
of anti-obesity medications inadolescents and advocacy work to ensure
equal access of treatments to all.
Welcome to the show.

Justin Ryder, PhD (01:12):
Thanks for having me, Erin.

So let's start off this episode by you sort of
setting the record straight foreveryone and defining obesity.
What is obesity?

Obesity, in my opinion, and in the opinion of about 35
medical organizations, it's a disease.
It's not a behavior.
I think of it as a complexgene environment interaction.
And when you have susceptible geneticsand a toxic environment, like we
all live in, it perpetuates obesity.

(01:43):
And there's tremendous biologicalunderpinning and etiology of
obesity and it's tremendouslyimpacted by our behaviors, but
behaviors do not drive weight.
It's really the biology

And this is something that you are passionate about sharing
with your providers at Lurie Children'sand also fellow investigators.
Is that right?

Absolutely, I think, you know, from an educational standpoint
obesity curriculum and medical trainingover the past several years has caught
on to this, but most pediatriciansand adult medical providers were not
trained that obesity was a disease.
They were trained that it was abehavior and that you could learn
how to treat obesity by exercisingmore and dieting and eating better.

(02:31):
That's been our approach, ourpublic health approach, certainly
for the last 40 plus years.
I don't think it'sreally worked very well.

So you mentioned obesity.
It's a chronic disease that'svery common in the pediatric
population, impacting approximately15 million children in the U.
S.
alone.
What are some of the health risks thatare associated with childhood obesity?

So obesity places children at higher risks for developing

a whole host of comorbidities (02:56):
pre diabetes, diabetes on the cardiovascular
side of things, hypertension,dyslipidemia, hypertriglyceridemia, but
also has a strong connection with nonbiologically based things like mental
health disorders, some of which arebiologically based and some of which
are not, depression, anxiety, increasedsuicidal ideation, lower quality of life,

(03:20):
and then also musculoskeletal limitations,big bodies are hard on joints.
And so, there are a lot of short termchallenges of obesity, but some of
these become long term problems as well.

So you mentioned these biological things,
these non biological aspects.
Are there specific culturalor societal factors that also
contribute to childhood obesity?

Yeah, absolutely.
Structural racism has definitelycontributed to childhood obesity.
There is a strong genetic componentin certain families and, racial and
ethnic groups, so children that comefrom Hispanic Latino families and
Black and African American familiesare disproportionately impacted by the

(04:05):
disease of obesity as well as some of thechronic diseases associated with obesity,
especially hypertension and diabetes.
And so there's definitely a socialand ethnic component to obesity.

What are some of the effective treatments
for childhood obesity?

The American Academy of Pediatrics put out new
clinical practice guidelines last year.
It came out in January.
They said some things very clearly inthere, so I'll distill the 135 plus
page document down really clearly.
One, obesity is a disease.
Two, watchful waiting is a practicethat we should not endorse anymore.

(04:46):
And what that means is childrenare not going to grow out of this.
Once you develop obesity, thelikelihood of you growing
out of it is very, very low.
And so what we need to do is treatit and treat it aggressively.
Anybody who has a BMI above the 85thpercentile, which is overweight
should be considered for some formof obesity prevention or treatment.

(05:08):
And those really fallinto three categories.
So there's intensive behavioralmodification and lifestyle modification.
The recommendation is 26 contacthours within a given year.
It's very, very challenging for providersto deliver in tertiary care settings
like we have at Lurie Children's Hospital,but also in the community and local

(05:29):
pediatricians, nobody can really do that.
It's really, really hard.
Then we have a number of anti-obesitymedications, so medications that
treat the underlying pathophysiologyof the disease of obesity.
There's a number of them that areFDA approved for ages 12 and up, as
well as several that are approved inadults that they're in the pipeline
and being studied in pediatrics.

(05:49):
And then we also have Bariatricsurgery, and bariatric surgery is
also an extraordinarily effectivetreatment for obesity, but also the
underlying other comorbidities thatare associated with obesity, bariatric
surgery also treats very effectively.

I want to talk more about the weight loss medications,
especially the new ones on the market.
Tell me about this new class of weightloss drugs and how they work in children.

So we're really at a extraordinary time where for
about 30 years, we didn't have verymany medications that were safe
and effective for treating obesity.
And if they were effective, theefficacy was rather small, on
average 5 percent weight loss.
Over the past several years now, wehave several medications that have

(06:37):
been FDA approved in adults and nowa couple that are FDA approved in
pediatrics that carry weight lossesof 10, 15, 20 percent on average.
It's an exciting time to be in thespace because we actually have real
treatments that really work, thattreat the underlying biology and
provide individuals with a tool to besuccessful on their weight loss journey.

(07:01):
One of the challenges we have,though, is those medications
are extraordinarily expensive.
And not a lot of insurances are coveringthem, and if they are covering them,
it's still a burden on patients andfamilies because the out of pocket
costs, even with coverage, can be high.
Nevertheless it's not to say thatthose drugs won't come down in cost
as more are added to the pipeline.

(07:23):
And we have more tools in our toolbox,but it's really shifting and changing
the landscape of obesity treatmentin both children and in adults.

And the brand names of those drugs are Wegovy and ZepBound.
Is there another one as well?

Yeah.
Wegovy, ZepBound, and Saxenda.

But states have been clamping down on coverage of any
sort for a lot of these medications.
I think just 16 states offer access toanti-obesity medications through Medicaid.
Tell me about how big of abarrier this is for patients
who want to try these new drugs.

Right, and so I think of that as a health equity
issue more so than anything else.
For instance, at Lurie Children'sHospital, the kids with obesity,
60 percent are covered by Medicaid.
And right now, until hopefully nextmonth Medicaid does not allow access
to any anti-obesity medications.
I mean, 60 percent of the kids thatprobably reside in Illinois, if we

(08:20):
extrapolate and think that, youknow, that's a comparable number,
have limited access to care.
And nationally, there's a numberof states, 35 or so, that have no
coverage for anti-obesity medication.
So any kid that's on Medicaid or adultthat's on Medicaid would not have
access to any anti-obesity medications.

(08:41):
But there are statesthat have it approved.
It's really unfortunate thatare scaling this back as well.
So North Carolina and Texas just announcedthat they are going to scale back their
coverage of anti-obesity medicationsbecause it was costing them too much.
And so it's really this delicatebalance of doing the right thing from
a health equity perspective and fortreating people with a real disease

(09:04):
as effectively as possible and cost.

And you've been involved in advocating for Illinois
Medicaid to cover these anti-obesitymedications for children and adults.
And this has been effective.
Tell me about this work.

Yeah, so I joined Northwestern and Lurie Children's
Hospital in January of 2023.
One of the first things I did was useour extraordinarily impactful government
affairs office here at Lurie Children'sHospital to help connect me with the
right people at Medicaid and within thestate to start to have these important

(09:36):
conversations about why they shouldbe covering anti-obesity medications,
to educate them about the disease ofobesity and how having access to these
tools and medications is a healthequity issue, but also could be cost
savings for the state but also the rightthing to do to cover these medications.

(09:57):
So we've been successful in thoseefforts and the new class of medications,
the GLP-1 receptor agonists willbe covered by Illinois Medicaid,
hopefully in March of this year.

So once these are covered by Medicaid coverage, what impact
do you foresee this is going to haveon treatment of obesity in Illinois?

Well, right now at Lurie Children's, the majority
of kids that are in our weightmanagement clinics are on Medicaid.
They have no access to any medicationsat all, so it could totally change
their treatment course and path,because right now it's two buckets.
It's lifestyle or it's surgery, andwe add a third treatment option, which
is going to be very, very powerful.

(10:37):
In adults it's going to be the samething or people that may have been
trying to pay for some of thesemedications out of pocket now will
have a pathway to do so that's lessfinancially burdensome to them.

Can you talk a little bit more about why it's important to address
this cost issue with the obesity drugs?
And there have been some studies thathave been published that were looking
at the cost effectiveness of thisdrug, and you wrote some commentary
to respond to one of these studies.
And you were quite passionate to pointout that these drugs are working in teens

(11:11):
and that, yes, the cost is something thatwe need to take into consideration, but
tell me some of your perspective on this.

Any cost effectiveness study that's done in
pediatrics on anti-obesity medications,in my opinion, is premature.
Because we only have one year data onthese medications, and to really look
at effectiveness and cost, you needfive, ten year studies because you
need a duration of the effects, durationof the costs, and right now we're
studying medications that are brand new.

(11:38):
They're really expensive,because guess what?
The drug companies put hundreds ofmillions, if not billions of dollars
to develop these medications andthey need to recoup their costs.
We wouldn't criticize somebodyfor having a high price of a new
cancer drug that treats cancer.
Yet these new anti-obesitymedications, everybody's up in arms
about the cost of the medications.

(12:01):
If insurance would cover thembetter, maybe we would be having
less of this conversation . Andthen the other challenge is.
is when you do a cost effectivenessanalysis, they take into
account the wholesale cost ofthe medication, not actually what
the consumer direct price is.
So you and I, if our insurance coversWegovy, it's not costing us 1,300 a month,

(12:23):
it's costing maybe 100 a month, right?
But so if you do a cost effectivenessanalysis of a drug that's 1,300 versus
Phentermine, for instance, which hasbeen FDA approved since 1958 and costs
$5, whether insurance covers it or not,of course, that drug's going to be more
cost effective because it's dirt cheap.
But it doesn't mean that it'sbetter medication, right?

(12:46):
And so any conversation alongthose lines needs to be balanced
with the current environment.
Of course, new drugs to market are goingto be very expensive, but it doesn't
mean that they're not worth using.

It's important to note that longitudinal research is
critical for understanding the long termeffects of anti-obesity medications.
What gaps in research do youbelieve need to be filled?

Yeah, it's a critical gap in pediatrics and one thing we
get criticized for all the time.
So the longest duration studies wehave in pediatrics for anti-obesity
medications are a little over a year.
So we definitely need to continue tostudy these medications long term and
we're not talking about one or twoyears, but five, ten year effects of

(13:30):
being on anti-obesity medications.
Study real world outcomes of thesemedications, working with our
pharmaceutical company partnersto really study the long term
implications both good and bad.
So we know what the risks are of beingon these medications and do we have a
beneficial you know, risk benefit ratio?

(13:51):
I fully believe that it'll show justlike we've shown with bariatric surgery,
that the long term implications of beingon these anti-obesity medications is
favorable but we need to understandthe risks so that we can educate
families, patients, and ourselves.
On what the implications of beingon these medications long term is.

One of the truths about these medications
is that this is a lifetimemedication, what we know right now.
Can you talk to me alittle bit about that?
And that's a concern that maybe somefolks have about starting a child on
a medication that may last for life.

it's a real conundrum.
I think as a medicalcommunity, we don't know.
We don't know if you need tobe on the medication lifelong.
There's actually a great study thatjust came out on Wegovy on what
happens if you've been on it fora year and then what happens the
next year when you're off of it.
And so it was a study thatwas done from 12, 000 people.

(14:48):
So it's a real world outcome studyof people that were on Wegovy for a
year and then off of it for a year.
And what happened was, Ithink, pretty remarkable.
I'm not going to give the exactpercentages, but it was 20 percent
stayed right about where their weight was.
Okay, so they kept everything off.
Twenty percent gained a littleor 20 percent lost a little.
So 60 percent were within sort ofa range of where they should be.

(15:13):
And then 20 percent were rightback to where they started.
But then there was also 20 percent whohad lost more weight than they had lost.
All over the board.
We call this heterogeneityor biological variability.
And so from a treatment perspective,it's actually kind of nice because
what that shows is that there'ssome people that actually don't

(15:34):
need to be on the medication longterm or for the rest of their life.
There's some people that actuallygive them that boost, give them
that success, allow them to resetmaybe their physiology a little bit.
And they might be able to keep it off.
Maybe that's 40 percent of people.
Then there might be another 40percent of people who, maybe we
could down titrate the medication.

(15:56):
Maybe they don't need to be on themaximal dose of that medication.
Maybe they could be on halfthe dose that they were on.
But then there might be 20 percentthat they might need to stay on
it for the rest of their life.
But we don't really know who thosepeople are, what proportion they
are, and with which medicationswe might be able to do this.
So it's a ripe area for study,there's a lot of people that are

(16:18):
pursuing that sort of question.
It really brings home sort ofsome precision medicine aspects.
And we're just getting to the pointwhere we can start to study that
with these new obesity medications.

Well, one area of obesity treatment where we do have a lot of data
and information is bariatric surgery.
And on a previous episode of this podcast,we had your longtime collaborator, Dr.
Thomas Inge, who's a professor ofsurgery at Feinberg and surgeon in chief
in the Department of Surgery at LurieChildren's, he came on and was talking
about the teen longitudinal assessmentof bariatric surgery study or teen labs.

(16:51):
Tell me about your collaborations with Dr.
Inge on looking at bariatricsurgery outcomes in teens.

So I've been really grateful for the opportunity
in collaboration with Dr.
Inge to work on teen labs for almost10 years now, and we're about ready to
actually publish our 10 year findings.
But what we've shown is that adolescentbariatric surgery is safe and it's
effective at treating not just obesitywhere mean mean weight loss at a

(17:18):
year with both Roux-en-Y gastricbypass and sleeve gastrectomy is
around 30 to 35 percent weight loss.
But also is effective at treating manyof the comorbid conditions such as
diabetes, pre diabetes, hypertension.
It's associated with obesity atabout a 70 percent success rate
across the board of all comorbidities.
And then it's also durable.

(17:39):
So out to 10 years, weight loss onaverage is still 20 percent from
where they were to begin with.
So better than most of the anti-obesitymedications get in one year.
And we're showing that fromone surgical procedure out to
10 years is quite remarkable.
And we still have quite durable resolutionof a lot of those comorbid conditions.

(18:01):
But there are some risks.
So with any study, we need to lookat what's good and what's bad.
And so there are some risks.
So there are some nutritional deficienciesand team labs really help set some of
the guidelines on how surgeons shouldbe prescribing vitamins and multivitamins
in the post surgical setting.
We're also really interested in bonehealth, because we don't want to set

(18:23):
kids up for early osteoporosis becausethat's been shown in adults, and
we're not necessarily seeing the samesignal in adolescents, but we have
to continue to study this, and it'sreally important that we do this work.

Are we going to be able to borrow some of the methods and some
of the ways that you've studied bariatricsurgery and apply that to these weight
loss drugs and the outcomes in kids?

I certainly hope so.
I hope that the NIH funds us to doit 10, 15 year study of anti-obesity
medication to understand the goodand the bad so that we can inform
guidelines, inform care in an appropriateway with appropriately designed study.
Whether or not it's NIH or industryfunding, a study of that nature,

(19:08):
it's absolutely vital thatwe study long term outcomes.
Both good and bad, so that wecan inform clinical practice, but
inform also the people that aregoing to be taking these potential
medications for a number of years.

Tell me about some of the projects that you're currently working
on that fall into these categories.

Yeah, so right now we're really fortunate to have some good
support for some of our ongoing research.
So we have one NIH funded study that'slooking at this question of why is it
so hard to keep weight off in kids?
So after kids have successfully lostweight, what's the biology and behavioral
mechanisms that are driving weight regain.

(19:48):
So we have funding to study that in acohort of adolescents that are in puberty,
which is a really strange time periodfor the kid going through it, for their
families, but also from a biologicalperspective, there's a whole lot going on.
We have funding from the NIH to do astudy looking at a diabetes medication
and seeing if it can treat obesity andwhat we call steatotic liver disease.

(20:12):
So when you have a lot of fat that'sinfiltrated the liver it's sort of
a very difficult area for treatment.
And there's a lot of adult studiesthat are focused on treating NASH or,
or, or steatotic liver disease, butthere's not a lot of pediatric studies.
So we're we have a study going onand we're trying to get funding and
actively pursuing a study where wewould love to do the first randomized

(20:37):
trial of some of the newer anti-obesitymedications versus bariatric surgery,
because the question always comesup, should I try the new medications
that cause maybe 15, 20, 25 percentweight loss, or should I have surgery?
We don't know the answer to that question,and we need to have a rigorously designed

(20:57):
study to, to be able to provide thatevidence base for clinicians, but also
patients and families, which therapiesmight be best, what are the, what's the
risk and benefit of those two, and youcan't do that until you have a rigorous,
randomized clinical trial, and so we'reactively trying to get that funded.

What would your hope be for the generation of
kids who are being born right now?
And they're being born into thisenvironment where obesity rates are high,
but new treatments are on the horizon.
What's your hope for them?

Yeah, so right now about 20 percent of kids in the U.
S.
have obesity, and we've seen anincrease in prevalence from 5 percent
in the 1980s to now where it's 20percent the 2020s, if you will.
I'd like to see in the next 40 years uscut that in half and go back down to 10%.
If we did that, I would be so happy, Iwould love to put myself out of a job.

(21:51):
How about that?

Well, thank you so much, Dr.
Justin Ryder, for being on theshow and for sharing all this
exciting work that you're doing.
We appreciate your time.

Thank you.

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