March 19, 2024 • 34 mins
Please join our special guest Dr. Ian Neeland from University Hospitals in Cleveland, to discuss the intersection of obesity and cardiovascular disease, and specifically the roles of the new agents semaglutide and tirzepatide. We discuss the recent data on cardiovascular outcomes with these agents, assessing patient candidacy, and tips for initiating and monitoring therapy. We also reviewed the complementary role of bariatric surgery and pharmacotherapy to improve cardiac outcomes.
For more information, see the SELECT study.
For more information about the UH CINEMA program, click on this link.
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Episode Transcript
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Kanny (00:12):
So welcome back everyone to the CardioHop podcast.
We're excited today to have adiscussion about metabolic
aspects of, of obesity and theintersection with heart disease.
And we're going to talk a littlebit about some new agents that
have been very popular in thecardiac world and the general
(00:32):
medical world as well, as wellas with the lay public in the
management of overweight andobesity.
I want to start first byintroducing as my cohost
familiar Voice to many of youDr.
Alan Sabic, who's a cardiacimaging specialist at University
Hospital.
Alan, thanks for joining ustoday.
Ellen (00:54):
Well, thank you I actually am really pleased and
honored to introduce Dr.
Ian Neeland, who is ourdiscussant today, who is a
colleague of mine here up inCleveland.
He is the director of UniversityHospital's Center for
Cardiovascular Prevention.
As well as the co director forUniversity Hospital's CINEMA
program, which is amultidisciplinary
(01:14):
cardiometabolic program herewithin the cardiology
department.
In addition to that, he is partof the American Heart
Association's multidisciplinarytask force and writing committee
on cardiovascular, kidney, andmetabolic syndrome.
But first, I wanted to ask Ian,could you tell us a little bit
about your career path as acardiologist who now is really
(01:36):
focusing on obesity and diabetesand intersection of that with
cardiovascular
Ian (01:42):
disease?
Sure.
Well, thanks for having me.
It's a pleasure to be on the, onthe podcast with you all.
I, I first got interested incardiometabolic disease, the
nexus between cardiovasculardisease, diabetes, and obesity
when I was a fellow.
I went to University of TexasSouthwestern Medical Center for
(02:03):
fellowship and had phenomenalmentors, including James Delimas
and Amit Khera.
And when I went there, I startedactually at a T32 where I would
do 2 years of research up frontand then 2 years of clinical
work and I plan to go and dowork in biomarkers.
At the time Dallas Heart Studywas ongoing and there were lots
(02:27):
of different biomarkers to lookat.
And the kind of the biomarkercraze was at its peak.
And so when I got there, itturned out that I wasn't able to
study biomarkers in the way thatI, I had planned and so I had to
pivot pretty early on in mytraining and figure something
out of what to do next.
(02:47):
So my mentor James DeLimas, herecommended considering looking
at what's called adiposopathy.
There was a an article that wasin Jack called adiposopathy or
sick fat by a researcher namedHarold Bayes.
And the concept of sick fat wassuch that body fat or adipose
(03:09):
tissue was actually an activeendocrine organ.
Not some inert storage centerwhere you just stuck
triglycerides and and went onyour day.
And there was an idea that therewas heterogeneity in patients
living with obesity, how itmanifested, some people get
diabetes and heart disease.
who have obesity and others donot.
(03:31):
And and what underlies thatquestion and that observation is
that some fat is sick fat andsome fat is quote unquote
healthy fat in the sense that itdoesn't exert the same adverse
metabolic effects as as otherfat.
And my research then was reallyfocused on trying to understand
(03:51):
the concept of sick fat, Why andwhere and led me to researching
body fat distribution as a keydriver of the cardio metabolic
consequences of obesity and ledme to the path to look at
visceral and ectopic fat that isfat that's in around the
internal organs as well as fatthat's in places where it
(04:12):
shouldn't be such as the liver,the heart, the kidneys and such.
And that led me then to be moreinterested in therapies, novel
therapies that impact body fatand especially by fat
distribution and led me tolooking into medications such as
SHLT2 inhibitors and agonists.
(04:34):
And then, that, that kind ofbroadened from there when these
medications.
For the first time became notonly anti hyperglycemic
medications for diabetes, butalso for obesity and
cardiovascular disease andkidney disease.
And so it's really been a anamazing kind of run since I
started as a fellow looking intothese concepts and really it's
(04:59):
still, still going.
I don't think we've reached apeak in any, any, any sense of
the word for the, thesecompounds that are coming out
and new therapies and novelthings where the intersection
between cardiovascular disease,diabetes, and obesity has never
been as great as it has istoday.
So it's really fun to be in thefield right now.
Kanny (05:19):
Well, thanks, Ian.
That sounds like quite a journeyto where we are now, we have an
audience today of, cardiacpractitioners, including
cardiologists.
Cardiac practitioners as well.
many of us work on the frontlines of kind of bread and
butter heart disease.
And of course, we see thecontributing effects of obesity
every day, in our clinicalexperience.
(05:40):
But how do you frame, like, therelationship between weight
metabolic dysfunction, and heartdisease in terms of,
contributing effects versuscausative effects?
Ian (05:50):
So I mentioned visceral and ectopic fat as a as the driver
for most of the cardiometaboliccomplications of obesity.
And I really do believe thatthere's a, a single central
pathophysiology that that drivesThat's a lot of the downstream
(06:10):
consequences and essentially itcomes from, excess body fat, but
that body fat, depending uponwhere you're, you store it as an
individual may impact down theline other surrogate
intermediate risk factors suchas hypertension, diabetes.
dyslipidemia, obstructive sleepapnea, chronic kidney disease,
(06:33):
all the different risk factorsthat we we know as intermediate
upstream of, of cardiacconsequences.
And so I think the, the best wayto think about it and frame it
is, is when you have a patientwho let's say has excess body
fat is maybe living withoverweight or obesity is to ask
yourself, how has thatmanifested in terms of risk
(06:56):
factors And if it has manifestedoften as a metabolic syndrome,
then that patients at three tofive times increased risk for
coronary artery disease, andprobably even higher risk for
heart failure, often with halfpath over half ref.
And and that's a patient thatreally requires aggressive risk
(07:19):
factor modification, notnecessarily in the sense that
we, picking off the individualrisk factors, but really
focusing on the, on the driver,focusing on the underlying
pathophysiology.
And often cases when you cantreat the visceral obesity with
either lifestyle pluspharmacologic therapy,
potentially with surgery, thenactually you mitigate a lot of
(07:42):
those intermediate risk factors,cure their hypertension, cure
their diabetes, resolve theirdyslipidemia, reduce their
cardiovascular risksubstantially.
And so I think a lot ofcardiologists myself included
before I was in this field feltlike, there's so many risk
factors to, to, to look at andthink about, that's really
(08:02):
should be the domain of of theprivate primary practice doctor
or the family doctorendocrinologist.
But but no longer really is thedomain of the cardiologist and
having a good sense of how youcan impact that central
pathophysiology can really go along way for not just primary
(08:22):
prevention for your patients,but secondary prevention as
well.
So I think thinking in thatframework is very helpful.
Ellen (08:30):
So, Ian, I know that you have done an awful lot with our
cinema program here, thismultidisciplinary program.
Can you explain to our audiencea little bit about how that is
set up, how it works?
And also, I know you've got somedata on at least two year
outcomes and sort of explain thebenefits of a type of program
Ian (08:48):
like this.
Sure.
I mean the cinema program reallydoes try to address the issue
that I that I just mentioned istrying to attack that central
pathophysiology and reducecardiovascular risk through
treatment of my cardiometabolicsyndrome.
The cinema program is one of agrowing number of programs in
(09:09):
the country.
There's, there's only a handfulout there.
And we're one of the firstactually with founding members
of the cardiometabolic careAlliance, along with.
St.
Luke's Mid America in KansasCity, where we wanted to come up
with a paradigm and a care modelthat was different than the
usual siloed individualspecialist care model where a
(09:32):
patient would go from specialistto specialist to take care of
this organ system and that organsystem and without any real,
understanding of the interplayand complexity between these
things, like, the patient has anendocrinologist, a primary
doctor, a cardiologist, anephrologist.
Well, really, a lot of thesephysiologies are interconnected
(09:53):
and linked.
And so we really wanted tochange the model and, be a
disrupter in that field.
And create a situation where,where we would provide
multidisciplinary comprehensivecare to patients with type two
diabetes or prediabetes andelevated cardiovascular risk.
And we would then be veryaggressive with evidence based
(10:15):
therapies.
Be very aggressive withlifestyle modification and use
full support of our team,including a nurse navigator, a
certified diabetes educatorspecialist, a dietitian, a
pharmacist champion as well as asignificant amount of
educational resources, includingzoom calls and support groups
(10:35):
and and online education.
And so the goal really was toimprove reduce cardiovascular
events.
Through improvement in thepatient's overall metabolic,
cardiometabolic health.
And so we started the program inMay 2020 and we've now, we're
now into our third and fourthyears, almost four years into
(11:00):
our fourth year.
And so we published our one yeardebt data and a journal American
Heart Association and our twoyear data in the journal of the
American Preventive CardiologyJournal.
And we've seen that even inpatients are in our program on a
median, let's say about six,seven months that they have
substantial reductions inweight.
(11:20):
blood pressure, LDL cholesterol,triglycerides urinaldehyde
claritinine ratio A1c,hemoglobin A1c.
They and they get on evidencebased therapies like SHLT2
agonists three, three fold morethan they would when they came
in.
And these are patients who haveseen endocrinology for years,
(11:41):
have primary care physicians whoare managing them.
And the, the issue is thatpeople, most people don't have
the time or resources to spendwith patients to be very
aggressive and, and the followup that's needed to help people
maintain, very very high levellifestyle modification care and,
and, and get the access to themedications, these life saving
(12:04):
medications that we have.
And so we're very proud of ourprogram.
We're expanding substantially.
We have.
Currently four sites, we'regoing to six sites actually is
coming here adding additionalpersonnel, including advanced
practice provider and a coupleof their MDs.
And and so, this is really thenew model.
This is the model that the HAhas has said is the, is the
(12:27):
future so I encourage people ifthey're interested to, to read
the papers and, see how themodel works.
And it's definitely,implementable.
In health care systems.
I've talked to lots of differentdoctors, not just in Ohio, but
in other states as well abouthow to implement care models
such as ours in cinema andpeople are doing it and they're
(12:50):
joined the alliance and gettingon board with, standardized
algorithmic care.
And there's studies that arebeing presented and published to
look at these.
So I think it really is thefuture of cardiovascular care.
Yeah, I
Ellen (13:05):
think we've shared several patients and I think
this multi disciplinary aspectis really quite crucial because,
individual practitioners don'tusually have time for the degree
of education that is needed forthe pharmacologic support, both
getting prior authorizations andalso, Holding the patient's
hands, going through certainside effects and stepping up
(13:26):
doses.
So what your group has reallyaccomplished is, is, has been
really quite incredible.
Kanny (13:33):
Yeah, thanks.
And I would second that as well.
I know how hard it is to get amultidisciplinary program, off
the ground and functional,especially, since some of these
lifestyle.
And other modifications don'tget, the same attention that,
that other therapies do in termsof reimbursement and so forth.
So congratulations on that andwe will put some links, to your
(13:55):
program in our notes as well.
I do want to make sure we havesome time to talk about, some of
the newer therapies that you'veput out.
Do offering your clinic andthat, of course, we've all been
hearing about in and both themedical literature and in the
lay media as well.
I know, GLP one Agnes have beenaround many years.
There have been studiesdocumenting their efficacy and
(14:18):
diabetic patients.
Why do you think some of the newdata such as a select study is
so relevant to cardiologists interms of how this can be a
direct benefit to our cardiacpatients.
Ian (14:30):
Sure.
So GLP ones are fascinating.
The they started out much likeSGLT2 inhibitors as medications
for diabetes.
improving glycemia focus on A1Creduction.
And it was only because theyhave, quote unquote side effects
or additional effects such asweight loss that people became,
(14:51):
become interested in them.
And when the LEADER trial cameout, which is a trial that was
done on the araglutide, which isone staley araglutide or Victoza
given to patients with type twodiabetes.
It was it was the first GLPreceptor agonist trial to show
cardiovascular benefit toreduce, cardiovascular events
(15:12):
and and that came around thesame time as some of the issues
of two inhibitor trials andcardiovascular outcomes.
And, this just blew up thefield.
And so since that time, therehave been several agonists that
have shown cardiovascularbenefit in diabetes patients and
once kind of that wasaccomplished the field moved on
(15:34):
to what about patients just withobesity?
Without diabetes, understandingthe essential, major risk factor
of obesity for cardiovasculardisease can candy.
Candy medications independent ofglycemic control impact
cardiovascular disease throughvis a vis through weight loss.
And this, this could be born outof look ahead trial, which was a
(15:56):
trial and type two diabetes andlifestyle modification to reduce
body weight where they were ableto get about 8 percent body
weight loss after the firstyear.
These patients and improveintermediate risk for risk
factors, but actually there wasno difference cardiovascular
events.
And so the big question, thefield was, just do you need more
weight loss to impactcardiovascular outcomes, or is
(16:18):
it how you lose the weight,through through a glp one
receptor agonist, for example,to impact it.
And so the select trial wasdesigned to, to actually answer
this question, patients livingwith overweight or obesity with
established cardiovasculardisease could giving the GLP 1
receptor agonist semaglutidewith a 2.
4 milligram dose once weeklyreally reduce cardio, hard
(16:42):
cardiovascular outcomes, right?
Major adverse cardiovascularevents, MACE.
And indeed, even despite arelatively modest weight loss of
about 9%, there was a 20 percentreduction in MACE events.
And so No, this became the firsttrial ever to show that treating
patients with obesity withoutdiabetes with a medication to
(17:04):
lower body weight reducedcardiovascular events.
And in fact, on Friday, just afew days ago the FDA added and
approved the label indicationfor semaglutide.
to reduce the risk of majoradverse cardiovascular events.
And to my knowledge, it's thefirst drug ever to have that
(17:25):
indication in, in a patientpopulation without diabetes.
So that's just the first thoughof, of ones that are, that are
coming down the pike.
There is the Trezepatide trial.
Trezepatide is interesting.
It's a dual agonist, GLP 1 andGIP.
And that's going to be looked atand surmount MMO.
(17:46):
That's a trial forcardiovascular outcomes.
And and then there's now atriple agonist out there that's
being developed not on themarket yet, which is a receptor
agonist for GLP, GIP andglucagon receptor.
And then there are severalothers that are in development
as well with the dual agonism.
So the field is really expandedsignificantly of trying to
(18:09):
harness the power of a creatinebased therapy and, and, and the
bodies on metabolism to to seeif it can actually improve not
just the metabolic pathways, butcardiovascular events.
And, and so that's the reasonwhy it's so important for, for
cardiovascular practitioners andspecialists is that just like
you give a patient a statin toreduce their cardiovascular
(18:30):
risk, not necessarily just treattheir cholesterol, just like you
give them, anti platelet therapyto reduce risk for another M.
I.
Not just to thin the blood.
So to you would give them a G.
L.
P.
One receptor agonist to reducerisk for mace, not just to treat
their obesity.
And that's why it really isimportant to to understand that
(18:53):
the medications and not justtreating obesity, but you're
treating cardiovascular disease.
And just as you would give lifesaving therapies to prevent, the
next MI, the next stroke youwould do the same here even
though it's also for weightloss.
So I think it's a, it's a frameshift that people have to have
in the cardiovascular field,understanding that it's, it's,
it's upon us as cardiovascularpractitioners to take up the
(19:15):
mantle and, and treat patientswith these evidence based
therapies that have, clearbenefits and indications.
So Ian,
Ellen (19:22):
one other question is, as far as we know, so many of our
obese patients have issues with,Heart failure with preserved
ejection fraction, not reducedejection fraction.
Can you touch base and give us afew lessons learned from the
STEP HF trial?
Using these medications toimprove HF preserved EF.
Ian (19:42):
Yes.
Yeah, sure.
No half path, right?
Heart failure, preservedejection fraction is, is the
next, kind of frontier ofcardiovascular care.
No, for many years we've hadtherapies that improve
mortality, morbidity, and haveref part failure for the juice
dissection fraction.
And we never had anything beyondblood pressure control and
(20:04):
diuretics for half path.
And then the issue to twoinhibitors came out.
As showing benefit and have pathand for heart failure
hospitalizations andcardiovascular death.
And and now we actually had adisease modifying therapy.
Well, it makes a lot of sensethat patients with half path who
have a lot of comorbidities suchas obesity, chronic kidney
(20:25):
disease.
hypertension and those patientscould derive benefit potentially
from something like a GLP 1receptor agonist.
So the STEP HF PEF trial wasperformed in patients without
diabetes.
There's actually one called STEPHF PEF DM that I'll be reporting
out soon for diabetes, but thisone was done in HEF PEF patients
(20:47):
without diabetes to see if itactually improved symptoms using
the Kansas City questionnaireKCCQ score.
And indeed as you might expectimproving body weight in
patients with overweight andobesity and HEF PEF did improve
symptoms to a substantialdegree.
And and so We don't currentlyhave outcomes trials with heart
(21:11):
failure hospitalizations, forexample, or, or cardiovascular
mortality with, with theseagents, but those will be
coming.
And I, and I could envision aworld where HEF PEF in the
future could be treated with anH22 inhibitor and agonist.
And and, and you'd have patientswith diabetes who are treated
the same patient withcardiovascular, atherosclerotic
(21:33):
cardiovascular disease treatedthe same.
And now.
patients with heart failure aretreated the same.
So, despite the fact that wehave so many different,
pathophysiologic mechanismsunderlying all these diseases,
it's coming down to a finalcommon pathway of a few, a few
classes of medications that havea pluripotent benefit for
cardiovascular and relateddiseases.
(21:54):
So it's really, it'sfascinating.
Fascinating stuff.
So keep an eye out for the STEPPEF PEF DM trial that I think is
going to be discussed at ACC, ifI'm not mistaken, or at ADA.
Kanny (22:06):
Yeah, that sounds really exciting.
And all of us who've beenstruggling with these patients
for so many years, it's great tosee more options with proven.
benefits coming down the pike.
Do you have any tips for ourcardiac practitioners?
clearly as you've outlined,there's a benefit here in many
of our patients, even the nondiabetic or at least the pre
(22:28):
diabetic patients.
Do you anticipate that, even ifwe see a patient who seems to be
a good candidate for either semiglutide or trizepatide, that it
could be initiated in a cardiacoperation?
Practice or would you, do yousee a more going through a multi
disciplinary clinic like the oneyou've created, given that
there's issues like cost andaccess to the medications and
(22:51):
the fact that they're given, nonorally as
Ian (22:55):
well.
Well, I think it's, it'scontextual just like anything
else.
I mean, if, if a cardiovascularpractitioner is is comfortable
with the medication,understanding how to use it,
when to use it, potential sideeffects, dose escalation, just
like you would, for example,with other injectables like
PCSK9 inhibitors or othertitratable medications like
(23:18):
Contresto, then I think forsure, that Doctors should try to
get an understanding of it andtry to use it.
it's, it's, it's not thatdifficult once you get the hang
of it.
there, the side effect profileis very is very easy to kind of
learn about and, and, and, andconsistent.
(23:38):
There's no usual surprises mostof it's GI side effects and
getting just understanding howto, how to manage those really
is 90 percent of the battle.
And then just kind of figureout.
kind of the nuances of betweeneach of the, of the drugs in the
class, but I, I definitely thinkthat cardiovascular docs and
(23:59):
providers should get familiarwith, with these, try to, try to
use them in their clinic.
They'll, as more, morecompetition comes out, more
trials come out and the drugcompany, the pharmaceutical
companies are able to get betterpricing and such.
It's going to be a bit easier, Ithink, and more acceptable to
get folks on therapies.
(24:20):
And so I would say, don't wait,to have someone go to a
multidisciplinary clinic likeours.
There are only a few across thecountry and, it's not, it, it,
it, patients could be waiting inlong lines.
And the other thing I would sayis that, patients are going to
go where they can get thetherapies, they know these
things work.
And so there's pop up shops.
(24:41):
That are really unregulated andgetting medications, not
necessarily from themanufacturer from, other places
or trying to, third party placesand selling it for, for cash
for, for, for low amounts ofmoney.
So patients will get these.
We'll get these drugs.
And I think that if, if we canprovide them as, in a safe
(25:02):
monitored environment as as, as,licensed practitioners, that
that's going to be safer for thepatients and better for
everybody.
So I would encourage people toread about it, to learn about
it.
just like anything else, onceyou get a hold of of potential
side effects and know how tomanage them, it's, it's it
becomes routine.
(25:22):
So one quick
Ellen (25:22):
question.
Are there any particular tricksand tips to initiate, well, two
questions.
One is getting approval throughthe insurance companies.
I know they used to be betterabout pre diabetics approving
them and now they're gettingvery strict about just
diabetics.
Do you think the fact that nowthat's been approved for with
the FDA for cardiovascular, doyou think that will?
(25:44):
broaden the approvals throughinsurance.
Ian (25:49):
I do.
I think I think eventually itwill happen.
I think there'll be a lag.
Part of the problem is that CMScurrently doesn't view obesity
as a chronic disease.
It's a behavioral condition.
And so there's a lot ofpolitical clout trying to trying
to convince the government thatobesity is a chronic disease and
(26:11):
needs to be managed like anyother chronic disease, like
diabetes or hypertension.
And so coverage for themedications, especially now that
there's a, an FDA approvedindication for cardiovascular
disease really should be thenext step.
And I don't know when that willhappen, but certainly if it
does, I think, I think to somedegree payers will, will follow
in line right now.
(26:33):
it's, it's pretty muchuniversally covered with or
without a prior authorizationfor patients with type two
diabetes.
And you're right.
It used to be pre diabetes waskind of, you can get it in
there, but they become morestrict and there are many
patients who have pre diabetesor, or even just, just with,
with obesity without prediabetes.
Who would be good candidates forthis medication and cannot get
(26:55):
it covered by their insurancecompanies.
paying out of pocket for thesecan be somewhere between 500 to
a thousand dollars a month.
It'd be very expensive.
And there's a lot of patients,unfortunately that we, we, we
can't provide therapy to becausethey just can't afford it.
Especially, patients, forexample, Medicaid, Medicare
patients who are in the donuthole becomes a real, a real
(27:18):
problem.
And these medications, they onlywork if you're taking them.
There's a, there's not really alegacy effect.
I mean, once patient stops themedication, there, there will be
weight regain not necessarilyall the way to the pre pre
medication weight, but there isweight regain and and also.
It's, you can't really switchbetween drugs in the class.
(27:40):
So there's a big shortage nowabout, for certain medications
used to be a big shortage forsemaglutide, then it switched to
Tirzepatide and back and forth.
And so, patients sometimes can'teven get the medications from
the pharmacy even if they couldafford it.
So it's still, still a lot to beworked out.
And at the, the, the rapidity ofgrowth of the, of the data
(28:03):
sometimes outstrips.
It outpaces the the, the abilityof society to keep up with
providing medications in anaffordable way.
So I think time will tell.
Kanny (28:14):
Question I have for you, Alan, actually, I know you
follow the literature prettyclosely for heart disease and
women and you have a practiceoften, skewed towards that as
well.
I know in this.
In this particular select study,one kind of potential criticism
was that only over 70 percent ofthe participants were men.
And of course, coronary diseasedoes present differently in men
and women.
(28:35):
So, Ellen, do you think, like,eventually we could apply this
more broadly to, women as well?
Or would, do you think the eventreduction would be similar?
Or is it just a matter ofstudying it more broadly in
larger groups to, to see thebenefits?
Well,
Ellen (28:51):
I, I think that we, we probably need to do a broader
study because I think for mostcardiovascular studies now we
really need to try andspecifically look at women.
However, I do think, with allthe mechanisms that Ian has
explained, I think it would makean awful lot of sense that we
should probably see similaroutcomes as far as improvement
(29:12):
in MACE.
So, I think, yes, we shouldstudy it more, but I think,
would I hold back on my womenpatients just because, well, we
don't have enough data?
No, absolutely not.
Because I, I do expect, I don'tknow if the exact magnitudes
would be the same, but I doexpect similar outcomes.
So I, I think there's a lot morestudying that can be done, but
(29:32):
boy, these are really excitingmedications with, broader and
broader applications as we'reseeing.
So, hopefully industry can keepup and provide the amount of
product that is needed.
Kanny (29:46):
Yeah, that makes sense to me too.
Well, we only have about fiveminutes or so left.
So, Ian one other question Ihave for you is, we obviously
have had access to another veryeffective therapy for obesity
for several years, which isbariatric surgery.
How do you see these new agentsWorking either in collaboration
(30:10):
or in conjunction withbariatrics and certain patients.
Do you think certain patientswould be candidates for one or
the other?
Or do you see them both beingused and various patient
populations to improve outcomes?
Ian (30:22):
Yes, I think it depends on the amount of weight loss
desired and needed for healthoutcomes.
And in terms of choosing whatthe best method would be, the,
the GLP one receptor agonist andrelated therapies.
Are really knocking on the doorof bariatric surgery related to
weight loss amounts.
we were talking about upwards of22 percent body weight loss,
(30:45):
whereas bariatric surgery is,usually between 30 to 40 percent
initially body weight loss atthe, at the maximal end.
So I think that if a patient,requires more than 20, 25% body
weight loss for whatever thehealth reason would be.
For example they're already on aGLP 1 plus other
(31:07):
antihyperglycemic medicationsand their diabetes is still not
well controlled, then bariatricsurgery usually is recommended
to reduce diabetes remission.
Sometimes it's the only thingthat can do it when someone's
maxed out, so to speak, onmedications or can't take
certain medications and theyhave, severe, moderate severe
obesity.
(31:27):
But whereas, patients who, whoreally kind of end up The mild
to moderate obesity range andthey really tend to 15 to 20
percent of body weight losswould be completely sufficient
to improve their health status.
Then I think pharmacologictherapy would definitely be
indicated.
I've seen situations ofcollaborative therapy, like you
mentioned, where.
(31:48):
A patient will go on a GLP 1 tolose weight and show that they
can lose and maintain to acertain degree before undergoing
bariatric surgery as a nextstep.
I've also seen situations wherea patient will have surgery and
then may gain some of the weightback.
And for maintenance therapy, goon a GLP 1 agonist.
(32:09):
So, I think there's a lot ofways to do it.
Obviously the GI side effectshave to be monitored very
closely when it's given inconjunction with breccic
surgery.
And also nutrition is a reallyimportant key.
To make sure there's nonutritional deficiencies,
vitamin deficiencies that canoften be seen with bariatric
surgery and and, to some degree,potentially GLP 1s if the
(32:33):
patient's not eatingappropriate, food intake, any
appropriate nutrition.
So yeah, I think, there's lotsof modalities out there now and
very effective modalities and Ithink as, as the procedural
complications are even lowermetric surgery than it had been
10, 20 years ago.
And we get more of the GLP onesin the market.
(32:53):
I think you're going to see acompetition between the two.
And what I'd like to seeultimately would be a trial, a
head to head trial.
in cardiovascular outcomes.
For the two, you don't have anycardiovascular outcomes trials
for batch of surgery in arandomized fashion.
That's all observational data.
I think that's also reallyimportant and really needed.
So there's a lot more work to dofor sure.
(33:14):
As when it goes to Patrick
Kanny (33:16):
surgery.
Well, yeah, it sounds likethere's just a lot of exciting
directions that this field isgoing.
And I think I think all of usand, and who deal with, cardiac,
cardiac patients every day are,are very appreciative to have
more and more options common.
I know we could talk quite a bitabout even more aspects of these
(33:37):
agents, but I think we are upagainst our time.
It sounds like, there's quite afew trials in progress, so I
look forward to maybe having youback in the future so you can
update us a little bit as thisfield evolves.
In the meantime, we will putsome links to the select study
as well as to some of Dr.
Nealon's publications.
(33:58):
Addressing his program as wellin our show notes, but I do want
to thank you both for joining usand taking the time to educate
us a little bit about theseagents.
Ian (34:09):
Yeah, my pleasure.
It's a it's been a real real funand happy to do it again.
Great.
Thank
Kanny (34:16):
you.
Kenny.
Yep.
Thank you both.
Thank you for joining today'spodcast.
For more information about thespeakers or the topics, please
go to Ohio acc.org,
So welcome back everyone to the CardioHop podcast.
We're excited today to have adiscussion about metabolic
aspects of, of obesity and theintersection with heart disease.
And we're going to talk a littlebit about some new agents that
have been very popular in thecardiac world and the general
(00:32):
medical world as well, as wellas with the lay public in the
management of overweight andobesity.
I want to start first byintroducing as my cohost
familiar Voice to many of youDr.
Alan Sabic, who's a cardiacimaging specialist at University
Hospital.
Alan, thanks for joining ustoday.
Ellen (00:54):
Well, thank you I actually am really pleased and
honored to introduce Dr.
Ian Neeland, who is ourdiscussant today, who is a
colleague of mine here up inCleveland.
He is the director of UniversityHospital's Center for
Cardiovascular Prevention.
As well as the co director forUniversity Hospital's CINEMA
program, which is amultidisciplinary
(01:14):
cardiometabolic program herewithin the cardiology
department.
In addition to that, he is partof the American Heart
Association's multidisciplinarytask force and writing committee
on cardiovascular, kidney, andmetabolic syndrome.
But first, I wanted to ask Ian,could you tell us a little bit
about your career path as acardiologist who now is really
(01:36):
focusing on obesity and diabetesand intersection of that with
cardiovascular
Ian (01:42):
disease?
Sure.
Well, thanks for having me.
It's a pleasure to be on the, onthe podcast with you all.
I, I first got interested incardiometabolic disease, the
nexus between cardiovasculardisease, diabetes, and obesity
when I was a fellow.
I went to University of TexasSouthwestern Medical Center for
(02:03):
fellowship and had phenomenalmentors, including James Delimas
and Amit Khera.
And when I went there, I startedactually at a T32 where I would
do 2 years of research up frontand then 2 years of clinical
work and I plan to go and dowork in biomarkers.
At the time Dallas Heart Studywas ongoing and there were lots
(02:27):
of different biomarkers to lookat.
And the kind of the biomarkercraze was at its peak.
And so when I got there, itturned out that I wasn't able to
study biomarkers in the way thatI, I had planned and so I had to
pivot pretty early on in mytraining and figure something
out of what to do next.
(02:47):
So my mentor James DeLimas, herecommended considering looking
at what's called adiposopathy.
There was a an article that wasin Jack called adiposopathy or
sick fat by a researcher namedHarold Bayes.
And the concept of sick fat wassuch that body fat or adipose
(03:09):
tissue was actually an activeendocrine organ.
Not some inert storage centerwhere you just stuck
triglycerides and and went onyour day.
And there was an idea that therewas heterogeneity in patients
living with obesity, how itmanifested, some people get
diabetes and heart disease.
who have obesity and others donot.
(03:31):
And and what underlies thatquestion and that observation is
that some fat is sick fat andsome fat is quote unquote
healthy fat in the sense that itdoesn't exert the same adverse
metabolic effects as as otherfat.
And my research then was reallyfocused on trying to understand
(03:51):
the concept of sick fat, Why andwhere and led me to researching
body fat distribution as a keydriver of the cardio metabolic
consequences of obesity and ledme to the path to look at
visceral and ectopic fat that isfat that's in around the
internal organs as well as fatthat's in places where it
(04:12):
shouldn't be such as the liver,the heart, the kidneys and such.
And that led me then to be moreinterested in therapies, novel
therapies that impact body fatand especially by fat
distribution and led me tolooking into medications such as
SHLT2 inhibitors and agonists.
(04:34):
And then, that, that kind ofbroadened from there when these
medications.
For the first time became notonly anti hyperglycemic
medications for diabetes, butalso for obesity and
cardiovascular disease andkidney disease.
And so it's really been a anamazing kind of run since I
started as a fellow looking intothese concepts and really it's
(04:59):
still, still going.
I don't think we've reached apeak in any, any, any sense of
the word for the, thesecompounds that are coming out
and new therapies and novelthings where the intersection
between cardiovascular disease,diabetes, and obesity has never
been as great as it has istoday.
So it's really fun to be in thefield right now.
Kanny (05:19):
Well, thanks, Ian.
That sounds like quite a journeyto where we are now, we have an
audience today of, cardiacpractitioners, including
cardiologists.
Cardiac practitioners as well.
many of us work on the frontlines of kind of bread and
butter heart disease.
And of course, we see thecontributing effects of obesity
every day, in our clinicalexperience.
(05:40):
But how do you frame, like, therelationship between weight
metabolic dysfunction, and heartdisease in terms of,
contributing effects versuscausative effects?
Ian (05:50):
So I mentioned visceral and ectopic fat as a as the driver
for most of the cardiometaboliccomplications of obesity.
And I really do believe thatthere's a, a single central
pathophysiology that that drivesThat's a lot of the downstream
(06:10):
consequences and essentially itcomes from, excess body fat, but
that body fat, depending uponwhere you're, you store it as an
individual may impact down theline other surrogate
intermediate risk factors suchas hypertension, diabetes.
dyslipidemia, obstructive sleepapnea, chronic kidney disease,
(06:33):
all the different risk factorsthat we we know as intermediate
upstream of, of cardiacconsequences.
And so I think the, the best wayto think about it and frame it
is, is when you have a patientwho let's say has excess body
fat is maybe living withoverweight or obesity is to ask
yourself, how has thatmanifested in terms of risk
(06:56):
factors And if it has manifestedoften as a metabolic syndrome,
then that patients at three tofive times increased risk for
coronary artery disease, andprobably even higher risk for
heart failure, often with halfpath over half ref.
And and that's a patient thatreally requires aggressive risk
(07:19):
factor modification, notnecessarily in the sense that
we, picking off the individualrisk factors, but really
focusing on the, on the driver,focusing on the underlying
pathophysiology.
And often cases when you cantreat the visceral obesity with
either lifestyle pluspharmacologic therapy,
potentially with surgery, thenactually you mitigate a lot of
(07:42):
those intermediate risk factors,cure their hypertension, cure
their diabetes, resolve theirdyslipidemia, reduce their
cardiovascular risksubstantially.
And so I think a lot ofcardiologists myself included
before I was in this field feltlike, there's so many risk
factors to, to, to look at andthink about, that's really
(08:02):
should be the domain of of theprivate primary practice doctor
or the family doctorendocrinologist.
But but no longer really is thedomain of the cardiologist and
having a good sense of how youcan impact that central
pathophysiology can really go along way for not just primary
(08:22):
prevention for your patients,but secondary prevention as
well.
So I think thinking in thatframework is very helpful.
Ellen (08:30):
So, Ian, I know that you have done an awful lot with our
cinema program here, thismultidisciplinary program.
Can you explain to our audiencea little bit about how that is
set up, how it works?
And also, I know you've got somedata on at least two year
outcomes and sort of explain thebenefits of a type of program
Ian (08:48):
like this.
Sure.
I mean the cinema program reallydoes try to address the issue
that I that I just mentioned istrying to attack that central
pathophysiology and reducecardiovascular risk through
treatment of my cardiometabolicsyndrome.
The cinema program is one of agrowing number of programs in
(09:09):
the country.
There's, there's only a handfulout there.
And we're one of the firstactually with founding members
of the cardiometabolic careAlliance, along with.
St.
Luke's Mid America in KansasCity, where we wanted to come up
with a paradigm and a care modelthat was different than the
usual siloed individualspecialist care model where a
(09:32):
patient would go from specialistto specialist to take care of
this organ system and that organsystem and without any real,
understanding of the interplayand complexity between these
things, like, the patient has anendocrinologist, a primary
doctor, a cardiologist, anephrologist.
Well, really, a lot of thesephysiologies are interconnected
(09:53):
and linked.
And so we really wanted tochange the model and, be a
disrupter in that field.
And create a situation where,where we would provide
multidisciplinary comprehensivecare to patients with type two
diabetes or prediabetes andelevated cardiovascular risk.
And we would then be veryaggressive with evidence based
(10:15):
therapies.
Be very aggressive withlifestyle modification and use
full support of our team,including a nurse navigator, a
certified diabetes educatorspecialist, a dietitian, a
pharmacist champion as well as asignificant amount of
educational resources, includingzoom calls and support groups
(10:35):
and and online education.
And so the goal really was toimprove reduce cardiovascular
events.
Through improvement in thepatient's overall metabolic,
cardiometabolic health.
And so we started the program inMay 2020 and we've now, we're
now into our third and fourthyears, almost four years into
(11:00):
our fourth year.
And so we published our one yeardebt data and a journal American
Heart Association and our twoyear data in the journal of the
American Preventive CardiologyJournal.
And we've seen that even inpatients are in our program on a
median, let's say about six,seven months that they have
substantial reductions inweight.
(11:20):
blood pressure, LDL cholesterol,triglycerides urinaldehyde
claritinine ratio A1c,hemoglobin A1c.
They and they get on evidencebased therapies like SHLT2
agonists three, three fold morethan they would when they came
in.
And these are patients who haveseen endocrinology for years,
(11:41):
have primary care physicians whoare managing them.
And the, the issue is thatpeople, most people don't have
the time or resources to spendwith patients to be very
aggressive and, and the followup that's needed to help people
maintain, very very high levellifestyle modification care and,
and, and get the access to themedications, these life saving
(12:04):
medications that we have.
And so we're very proud of ourprogram.
We're expanding substantially.
We have.
Currently four sites, we'regoing to six sites actually is
coming here adding additionalpersonnel, including advanced
practice provider and a coupleof their MDs.
And and so, this is really thenew model.
This is the model that the HAhas has said is the, is the
(12:27):
future so I encourage people ifthey're interested to, to read
the papers and, see how themodel works.
And it's definitely,implementable.
In health care systems.
I've talked to lots of differentdoctors, not just in Ohio, but
in other states as well abouthow to implement care models
such as ours in cinema andpeople are doing it and they're
(12:50):
joined the alliance and gettingon board with, standardized
algorithmic care.
And there's studies that arebeing presented and published to
look at these.
So I think it really is thefuture of cardiovascular care.
Yeah, I
Ellen (13:05):
think we've shared several patients and I think
this multi disciplinary aspectis really quite crucial because,
individual practitioners don'tusually have time for the degree
of education that is needed forthe pharmacologic support, both
getting prior authorizations andalso, Holding the patient's
hands, going through certainside effects and stepping up
(13:26):
doses.
So what your group has reallyaccomplished is, is, has been
really quite incredible.
Kanny (13:33):
Yeah, thanks.
And I would second that as well.
I know how hard it is to get amultidisciplinary program, off
the ground and functional,especially, since some of these
lifestyle.
And other modifications don'tget, the same attention that,
that other therapies do in termsof reimbursement and so forth.
So congratulations on that andwe will put some links, to your
(13:55):
program in our notes as well.
I do want to make sure we havesome time to talk about, some of
the newer therapies that you'veput out.
Do offering your clinic andthat, of course, we've all been
hearing about in and both themedical literature and in the
lay media as well.
I know, GLP one Agnes have beenaround many years.
There have been studiesdocumenting their efficacy and
(14:18):
diabetic patients.
Why do you think some of the newdata such as a select study is
so relevant to cardiologists interms of how this can be a
direct benefit to our cardiacpatients.
Ian (14:30):
Sure.
So GLP ones are fascinating.
The they started out much likeSGLT2 inhibitors as medications
for diabetes.
improving glycemia focus on A1Creduction.
And it was only because theyhave, quote unquote side effects
or additional effects such asweight loss that people became,
(14:51):
become interested in them.
And when the LEADER trial cameout, which is a trial that was
done on the araglutide, which isone staley araglutide or Victoza
given to patients with type twodiabetes.
It was it was the first GLPreceptor agonist trial to show
cardiovascular benefit toreduce, cardiovascular events
(15:12):
and and that came around thesame time as some of the issues
of two inhibitor trials andcardiovascular outcomes.
And, this just blew up thefield.
And so since that time, therehave been several agonists that
have shown cardiovascularbenefit in diabetes patients and
once kind of that wasaccomplished the field moved on
(15:34):
to what about patients just withobesity?
Without diabetes, understandingthe essential, major risk factor
of obesity for cardiovasculardisease can candy.
Candy medications independent ofglycemic control impact
cardiovascular disease throughvis a vis through weight loss.
And this, this could be born outof look ahead trial, which was a
(15:56):
trial and type two diabetes andlifestyle modification to reduce
body weight where they were ableto get about 8 percent body
weight loss after the firstyear.
These patients and improveintermediate risk for risk
factors, but actually there wasno difference cardiovascular
events.
And so the big question, thefield was, just do you need more
weight loss to impactcardiovascular outcomes, or is
(16:18):
it how you lose the weight,through through a glp one
receptor agonist, for example,to impact it.
And so the select trial wasdesigned to, to actually answer
this question, patients livingwith overweight or obesity with
established cardiovasculardisease could giving the GLP 1
receptor agonist semaglutidewith a 2.
4 milligram dose once weeklyreally reduce cardio, hard
(16:42):
cardiovascular outcomes, right?
Major adverse cardiovascularevents, MACE.
And indeed, even despite arelatively modest weight loss of
about 9%, there was a 20 percentreduction in MACE events.
And so No, this became the firsttrial ever to show that treating
patients with obesity withoutdiabetes with a medication to
(17:04):
lower body weight reducedcardiovascular events.
And in fact, on Friday, just afew days ago the FDA added and
approved the label indicationfor semaglutide.
to reduce the risk of majoradverse cardiovascular events.
And to my knowledge, it's thefirst drug ever to have that
(17:25):
indication in, in a patientpopulation without diabetes.
So that's just the first thoughof, of ones that are, that are
coming down the pike.
There is the Trezepatide trial.
Trezepatide is interesting.
It's a dual agonist, GLP 1 andGIP.
And that's going to be looked atand surmount MMO.
(17:46):
That's a trial forcardiovascular outcomes.
And and then there's now atriple agonist out there that's
being developed not on themarket yet, which is a receptor
agonist for GLP, GIP andglucagon receptor.
And then there are severalothers that are in development
as well with the dual agonism.
So the field is really expandedsignificantly of trying to
(18:09):
harness the power of a creatinebased therapy and, and, and the
bodies on metabolism to to seeif it can actually improve not
just the metabolic pathways, butcardiovascular events.
And, and so that's the reasonwhy it's so important for, for
cardiovascular practitioners andspecialists is that just like
you give a patient a statin toreduce their cardiovascular
(18:30):
risk, not necessarily just treattheir cholesterol, just like you
give them, anti platelet therapyto reduce risk for another M.
I.
Not just to thin the blood.
So to you would give them a G.
L.
P.
One receptor agonist to reducerisk for mace, not just to treat
their obesity.
And that's why it really isimportant to to understand that
(18:53):
the medications and not justtreating obesity, but you're
treating cardiovascular disease.
And just as you would give lifesaving therapies to prevent, the
next MI, the next stroke youwould do the same here even
though it's also for weightloss.
So I think it's a, it's a frameshift that people have to have
in the cardiovascular field,understanding that it's, it's,
it's upon us as cardiovascularpractitioners to take up the
(19:15):
mantle and, and treat patientswith these evidence based
therapies that have, clearbenefits and indications.
So Ian,
Ellen (19:22):
one other question is, as far as we know, so many of our
obese patients have issues with,Heart failure with preserved
ejection fraction, not reducedejection fraction.
Can you touch base and give us afew lessons learned from the
STEP HF trial?
Using these medications toimprove HF preserved EF.
Ian (19:42):
Yes.
Yeah, sure.
No half path, right?
Heart failure, preservedejection fraction is, is the
next, kind of frontier ofcardiovascular care.
No, for many years we've hadtherapies that improve
mortality, morbidity, and haveref part failure for the juice
dissection fraction.
And we never had anything beyondblood pressure control and
(20:04):
diuretics for half path.
And then the issue to twoinhibitors came out.
As showing benefit and have pathand for heart failure
hospitalizations andcardiovascular death.
And and now we actually had adisease modifying therapy.
Well, it makes a lot of sensethat patients with half path who
have a lot of comorbidities suchas obesity, chronic kidney
(20:25):
disease.
hypertension and those patientscould derive benefit potentially
from something like a GLP 1receptor agonist.
So the STEP HF PEF trial wasperformed in patients without
diabetes.
There's actually one called STEPHF PEF DM that I'll be reporting
out soon for diabetes, but thisone was done in HEF PEF patients
(20:47):
without diabetes to see if itactually improved symptoms using
the Kansas City questionnaireKCCQ score.
And indeed as you might expectimproving body weight in
patients with overweight andobesity and HEF PEF did improve
symptoms to a substantialdegree.
And and so We don't currentlyhave outcomes trials with heart
(21:11):
failure hospitalizations, forexample, or, or cardiovascular
mortality with, with theseagents, but those will be
coming.
And I, and I could envision aworld where HEF PEF in the
future could be treated with anH22 inhibitor and agonist.
And and, and you'd have patientswith diabetes who are treated
the same patient withcardiovascular, atherosclerotic
(21:33):
cardiovascular disease treatedthe same.
And now.
patients with heart failure aretreated the same.
So, despite the fact that wehave so many different,
pathophysiologic mechanismsunderlying all these diseases,
it's coming down to a finalcommon pathway of a few, a few
classes of medications that havea pluripotent benefit for
cardiovascular and relateddiseases.
(21:54):
So it's really, it'sfascinating.
Fascinating stuff.
So keep an eye out for the STEPPEF PEF DM trial that I think is
going to be discussed at ACC, ifI'm not mistaken, or at ADA.
Kanny (22:06):
Yeah, that sounds really exciting.
And all of us who've beenstruggling with these patients
for so many years, it's great tosee more options with proven.
benefits coming down the pike.
Do you have any tips for ourcardiac practitioners?
clearly as you've outlined,there's a benefit here in many
of our patients, even the nondiabetic or at least the pre
(22:28):
diabetic patients.
Do you anticipate that, even ifwe see a patient who seems to be
a good candidate for either semiglutide or trizepatide, that it
could be initiated in a cardiacoperation?
Practice or would you, do yousee a more going through a multi
disciplinary clinic like the oneyou've created, given that
there's issues like cost andaccess to the medications and
(22:51):
the fact that they're given, nonorally as
Ian (22:55):
well.
Well, I think it's, it'scontextual just like anything
else.
I mean, if, if a cardiovascularpractitioner is is comfortable
with the medication,understanding how to use it,
when to use it, potential sideeffects, dose escalation, just
like you would, for example,with other injectables like
PCSK9 inhibitors or othertitratable medications like
(23:18):
Contresto, then I think forsure, that Doctors should try to
get an understanding of it andtry to use it.
it's, it's, it's not thatdifficult once you get the hang
of it.
there, the side effect profileis very is very easy to kind of
learn about and, and, and, andconsistent.
(23:38):
There's no usual surprises mostof it's GI side effects and
getting just understanding howto, how to manage those really
is 90 percent of the battle.
And then just kind of figureout.
kind of the nuances of betweeneach of the, of the drugs in the
class, but I, I definitely thinkthat cardiovascular docs and
(23:59):
providers should get familiarwith, with these, try to, try to
use them in their clinic.
They'll, as more, morecompetition comes out, more
trials come out and the drugcompany, the pharmaceutical
companies are able to get betterpricing and such.
It's going to be a bit easier, Ithink, and more acceptable to
get folks on therapies.
(24:20):
And so I would say, don't wait,to have someone go to a
multidisciplinary clinic likeours.
There are only a few across thecountry and, it's not, it, it,
it, patients could be waiting inlong lines.
And the other thing I would sayis that, patients are going to
go where they can get thetherapies, they know these
things work.
And so there's pop up shops.
(24:41):
That are really unregulated andgetting medications, not
necessarily from themanufacturer from, other places
or trying to, third party placesand selling it for, for cash
for, for, for low amounts ofmoney.
So patients will get these.
We'll get these drugs.
And I think that if, if we canprovide them as, in a safe
(25:02):
monitored environment as as, as,licensed practitioners, that
that's going to be safer for thepatients and better for
everybody.
So I would encourage people toread about it, to learn about
it.
just like anything else, onceyou get a hold of of potential
side effects and know how tomanage them, it's, it's it
becomes routine.
(25:22):
So one quick
Ellen (25:22):
question.
Are there any particular tricksand tips to initiate, well, two
questions.
One is getting approval throughthe insurance companies.
I know they used to be betterabout pre diabetics approving
them and now they're gettingvery strict about just
diabetics.
Do you think the fact that nowthat's been approved for with
the FDA for cardiovascular, doyou think that will?
(25:44):
broaden the approvals throughinsurance.
Ian (25:49):
I do.
I think I think eventually itwill happen.
I think there'll be a lag.
Part of the problem is that CMScurrently doesn't view obesity
as a chronic disease.
It's a behavioral condition.
And so there's a lot ofpolitical clout trying to trying
to convince the government thatobesity is a chronic disease and
(26:11):
needs to be managed like anyother chronic disease, like
diabetes or hypertension.
And so coverage for themedications, especially now that
there's a, an FDA approvedindication for cardiovascular
disease really should be thenext step.
And I don't know when that willhappen, but certainly if it
does, I think, I think to somedegree payers will, will follow
in line right now.
(26:33):
it's, it's pretty muchuniversally covered with or
without a prior authorizationfor patients with type two
diabetes.
And you're right.
It used to be pre diabetes waskind of, you can get it in
there, but they become morestrict and there are many
patients who have pre diabetesor, or even just, just with,
with obesity without prediabetes.
Who would be good candidates forthis medication and cannot get
(26:55):
it covered by their insurancecompanies.
paying out of pocket for thesecan be somewhere between 500 to
a thousand dollars a month.
It'd be very expensive.
And there's a lot of patients,unfortunately that we, we, we
can't provide therapy to becausethey just can't afford it.
Especially, patients, forexample, Medicaid, Medicare
patients who are in the donuthole becomes a real, a real
(27:18):
problem.
And these medications, they onlywork if you're taking them.
There's a, there's not really alegacy effect.
I mean, once patient stops themedication, there, there will be
weight regain not necessarilyall the way to the pre pre
medication weight, but there isweight regain and and also.
It's, you can't really switchbetween drugs in the class.
(27:40):
So there's a big shortage nowabout, for certain medications
used to be a big shortage forsemaglutide, then it switched to
Tirzepatide and back and forth.
And so, patients sometimes can'teven get the medications from
the pharmacy even if they couldafford it.
So it's still, still a lot to beworked out.
And at the, the, the rapidity ofgrowth of the, of the data
(28:03):
sometimes outstrips.
It outpaces the the, the abilityof society to keep up with
providing medications in anaffordable way.
So I think time will tell.
Kanny (28:14):
Question I have for you, Alan, actually, I know you
follow the literature prettyclosely for heart disease and
women and you have a practiceoften, skewed towards that as
well.
I know in this.
In this particular select study,one kind of potential criticism
was that only over 70 percent ofthe participants were men.
And of course, coronary diseasedoes present differently in men
and women.
(28:35):
So, Ellen, do you think, like,eventually we could apply this
more broadly to, women as well?
Or would, do you think the eventreduction would be similar?
Or is it just a matter ofstudying it more broadly in
larger groups to, to see thebenefits?
Well,
Ellen (28:51):
I, I think that we, we probably need to do a broader
study because I think for mostcardiovascular studies now we
really need to try andspecifically look at women.
However, I do think, with allthe mechanisms that Ian has
explained, I think it would makean awful lot of sense that we
should probably see similaroutcomes as far as improvement
(29:12):
in MACE.
So, I think, yes, we shouldstudy it more, but I think,
would I hold back on my womenpatients just because, well, we
don't have enough data?
No, absolutely not.
Because I, I do expect, I don'tknow if the exact magnitudes
would be the same, but I doexpect similar outcomes.
So I, I think there's a lot morestudying that can be done, but
(29:32):
boy, these are really excitingmedications with, broader and
broader applications as we'reseeing.
So, hopefully industry can keepup and provide the amount of
product that is needed.
Kanny (29:46):
Yeah, that makes sense to me too.
Well, we only have about fiveminutes or so left.
So, Ian one other question Ihave for you is, we obviously
have had access to another veryeffective therapy for obesity
for several years, which isbariatric surgery.
How do you see these new agentsWorking either in collaboration
(30:10):
or in conjunction withbariatrics and certain patients.
Do you think certain patientswould be candidates for one or
the other?
Or do you see them both beingused and various patient
populations to improve outcomes?
Ian (30:22):
Yes, I think it depends on the amount of weight loss
desired and needed for healthoutcomes.
And in terms of choosing whatthe best method would be, the,
the GLP one receptor agonist andrelated therapies.
Are really knocking on the doorof bariatric surgery related to
weight loss amounts.
we were talking about upwards of22 percent body weight loss,
(30:45):
whereas bariatric surgery is,usually between 30 to 40 percent
initially body weight loss atthe, at the maximal end.
So I think that if a patient,requires more than 20, 25% body
weight loss for whatever thehealth reason would be.
For example they're already on aGLP 1 plus other
(31:07):
antihyperglycemic medicationsand their diabetes is still not
well controlled, then bariatricsurgery usually is recommended
to reduce diabetes remission.
Sometimes it's the only thingthat can do it when someone's
maxed out, so to speak, onmedications or can't take
certain medications and theyhave, severe, moderate severe
obesity.
(31:27):
But whereas, patients who, whoreally kind of end up The mild
to moderate obesity range andthey really tend to 15 to 20
percent of body weight losswould be completely sufficient
to improve their health status.
Then I think pharmacologictherapy would definitely be
indicated.
I've seen situations ofcollaborative therapy, like you
mentioned, where.
(31:48):
A patient will go on a GLP 1 tolose weight and show that they
can lose and maintain to acertain degree before undergoing
bariatric surgery as a nextstep.
I've also seen situations wherea patient will have surgery and
then may gain some of the weightback.
And for maintenance therapy, goon a GLP 1 agonist.
(32:09):
So, I think there's a lot ofways to do it.
Obviously the GI side effectshave to be monitored very
closely when it's given inconjunction with breccic
surgery.
And also nutrition is a reallyimportant key.
To make sure there's nonutritional deficiencies,
vitamin deficiencies that canoften be seen with bariatric
surgery and and, to some degree,potentially GLP 1s if the
(32:33):
patient's not eatingappropriate, food intake, any
appropriate nutrition.
So yeah, I think, there's lotsof modalities out there now and
very effective modalities and Ithink as, as the procedural
complications are even lowermetric surgery than it had been
10, 20 years ago.
And we get more of the GLP onesin the market.
(32:53):
I think you're going to see acompetition between the two.
And what I'd like to seeultimately would be a trial, a
head to head trial.
in cardiovascular outcomes.
For the two, you don't have anycardiovascular outcomes trials
for batch of surgery in arandomized fashion.
That's all observational data.
I think that's also reallyimportant and really needed.
So there's a lot more work to dofor sure.
(33:14):
As when it goes to Patrick
Kanny (33:16):
surgery.
Well, yeah, it sounds likethere's just a lot of exciting
directions that this field isgoing.
And I think I think all of usand, and who deal with, cardiac,
cardiac patients every day are,are very appreciative to have
more and more options common.
I know we could talk quite a bitabout even more aspects of these
(33:37):
agents, but I think we are upagainst our time.
It sounds like, there's quite afew trials in progress, so I
look forward to maybe having youback in the future so you can
update us a little bit as thisfield evolves.
In the meantime, we will putsome links to the select study
as well as to some of Dr.
Nealon's publications.
(33:58):
Addressing his program as wellin our show notes, but I do want
to thank you both for joining usand taking the time to educate
us a little bit about theseagents.
Ian (34:09):
Yeah, my pleasure.
It's a it's been a real real funand happy to do it again.
Great.
Thank
Kanny (34:16):
you.
Kenny.
Yep.
Thank you both.
Thank you for joining today'spodcast.
For more information about thespeakers or the topics, please
go to Ohio acc.org,
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