The Business & Science Behind the GLP-1 Boom

GLP-1 drugs have produced some of the most consistent weight loss results medicine has ever seen. The business of actually getting them to patients is a different story entirely.

David E. Williams, President of Health Business Group, and John Driscoll, Chairman of UConn Health, break down the CVS Caremark formulary reversal on CareTalk, examining what it reveals about the economics of GLP-1 coverage, and why emerging clinical research on cancer, long COVID, and addiction may push these drugs far beyond their original indication.

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Transcript

SPEAKER_00 0:00

CVS CareMark is restoring coverage of Zetbound, reversing a formulary decision from last summer that saved employers money but prompted patient anger and a class action lawsuit. It's a useful window into how GLP1 coverage is decided. We're going to also talk about the compounding market, the rise of microdosing, and the latest clinical research on GLP1s in cancer, long COVID, and beyond.

SPEAKER_01 0:37

And I'm John Driscoll, the Chairman of UConn Health. David, this is a great topic. Everybody's taking these drugs, and they seem to be miracle drugs. How could CVS CareMark have the Hutzpah to actually say no when the rest of America and apparently the clinical establishment is saying yes?

SPEAKER_00 0:57

Aaron Powell Well, John, I didn't know if you were going to go with Yiddish. I thought maybe you'd say temerity. There's a lot of words that could be it could be done there. I mean, what happens, I think, is that on the one hand, these drugs are great. On the other hand, you know, you're supposed to be managing the pharmacy benefit, which means just not just saying yes to everything and paying all this money.

SPEAKER_01 1:18

And so they said, hey, you got drugs that weren't a PBM. It isn't about saying no to everything either.

SPEAKER_00 1:23

I mean, come on. It isn't. So how could they do it? I mean, I think what happened is you had two drugs that were really great, and they saw a big financial opportunity, and they said, let's actually go for it. It was a little bit of a head scratcher for me, John, even at the time that they did it. Trevor Burrus, Jr. Like you? Yeah. Because they don't usually like to say no, like you said, especially if they're because there are differences between the products.

SPEAKER_01 1:47

But aren't they all the same?

SPEAKER_00 1:51

I'm not a physician. But uh no, they show different uh they sh they they show different results in trials.

SPEAKER_01 1:59

And when you're on your you the are the the the doctors who we do consult, what's interesting about the GLP ones as a category is they do appear to have, although generally the same opportunities for um uh weight reduction and all the other corollary stuff that that appears to be going well, and some of the similar clinical challenges, uh, that they do seem to the the different the different chemical composition appears to to have slightly different results. But as a category, Dave, wasn't the the miss here that they didn't embrace it? Because gosh, this seems to be these seems to be pretty remarkable drugs.

SPEAKER_00 2:43

Aaron Ross Powell I don't know, John. So I mean I I actually want to let's dwell on the financial aspect a little bit more, because the other thing that we're seeing is whether people bring on coverage because it seems like, well, it's a it's a drug that's gonna help somebody and it's also maybe gonna save money even in the near term. But then on the other hand, you see a lot of employers that are dropping coverage and health plans because they can't afford it. And I'm I'm assuming that what happened was CVS was trying to say, hey, employers, keep it on your formulary, keep a GLP one on your formulary, but we're gonna do something where we're gonna get you a good value and you're gonna be able to afford to do that.

SPEAKER_01 3:16

I mean, I do think it is between the So let's give let's give the PBMs uh uh some some credit here. The GLP one manufacturers, Lily, Novo, Nordisk, they were jamming people on price. I mean, they were clearly charging an extortionate amount initially. Well, you could see because they immediately were charging 70 to 80 percent less in the in like Europe. So you fly to London, you can pay for your Zeppelin prescription a few times over. But and so it punched a hole in the budget. Budgets for pharmaceuticals and healthcare are set a year before. That's when people underwrite. And so when you have this hugely popular drug that is very expensive and it's being relentlessly, you know, marketed by dancing people on TV, that the that there would be a you know uh a fear that the it would be a budget buster. And so, you know, you gotta you gotta give them some credit. But but these the and and and you know, we don't know yet, at least you know, last year, this is happening all in real time, that the prices would come down and the and the and the implications would be would be great. But why what else is behind that decision for CVS Care Mark and what's the state of play right now?

SPEAKER_00 4:39

Well, it sounded like there's actually a lawsuit that was alleging that there were ERISA violations. So people's rights are being uh affected. So I think that is probably a good reason uh for them to reverse course on that.

SPEAKER_01 4:52

And it's also just you know you can't just contextually for folks, most larger employers are self-insured. They're covered under ERISA, which is the the the federal exemption from local state insurance regulations, because most health insurance policies are regulated on a state basis. But for the large multi-state employers, there's something called an ERISA exemption, and they're covered under a different category. However, that the the the assumption is if you're paying a ton of money for health insurance, which everybody does, both the combination of out-of-pocket and the employer, that those health policies would promote your health, and the drugs that you would expect or that your doctor and others are prescribing would be covered as part of the health insurance that you're paid for. And so that's, I think, the basis of what that lawsuit was all about.

SPEAKER_00 5:45

I think there's a fascinating, I mean, as fascinating as these drugs are and their clinical impact, it's fascinating what's going on on the business side. Because you've got the typical dynamics uh here, let's say, between the PBMs, the employers, the drug companies, then you've also got the substantial consumer program because you've got the compounded drugs that people have essentially been shopping for on their own thing.

SPEAKER_01 6:07

Trevor Burrus, Jr.: What do you mean compounded drugs?

SPEAKER_00 6:09

Aaron Ross Powell Well, what I mean is that a there are pharmacies that are allowed to actually make the equivalent product in certain circumstances. And the circumstance here was there was a shortage of these name-brand products initially because it's insanely popular.

SPEAKER_01 6:26

Exactly. Um the the potential for diabetes, which is overwhelming, we've never seen diabetes in in such a large swath of the population, even getting down to kids. It used to be a disease of older people, uncontrolled sugar, too much food, leading to major weight gain and general. I mean, that's why these drugs were designed and they seem to work. They have they have remarkably consistent weight loss results. I mean, this this this is and and and and they were e they were very popular.

SPEAKER_00 7:16

Absolutely, John. And unlike some expensive products that are out there, these drugs are not actually expensive or complicated to manufacture. And so a compounder can basically get the raw ingredients and put something together that's similar. And when there was a shortage, they were allowed to do so. And so they built up a big business there. And then the shortage was declared over.

SPEAKER_01 7:41

So context here, then the the inputs are cheap. The price ceiling that Lily and Novo, the branded manufacturers, was very high. So these compounders, which is just a weird way of thinking, but think of it, the mortar and pestle that you'd see as a sign of people grinding things up and creating drugs, which hasn't been true probably since the time of of uh of the Greeks in terms of the way. But but you know, it is a is a is a is the is the sign of compounding. Became super popular, and then there were there was a lot of direct-to-consumer advertising because the compounders figured out that that the the big brand folks were having a lot of fun with the the all that direct-to-consumer advertising with mu cute ditties and people dancing and music seemed to really work. So they got into the game as well, and the compounding business exploded as well, because these drugs are, although there's a very high rate of people who quit using them for the pope people who for whom could tolerate it, it's they've been in in transformational in terms of people's health.

SPEAKER_00 8:51

So here's a weird thing that happened, John. So once the shortage period ended, and FDA declared, you know, it's not a shortage anymore, you can't make these products, the prescriptions for the compounded versions actually went up. And so IQVIA showed in, you know, so the compound the shortage period ended in February 2025, but then data from October 2025 shows that actually uh the number of prescriptions went up. And it's basically because it was affordable for people, and the compounders didn't want to get out of this business any too quickly. And they did a few things like make a dose that isn't exactly available or put vitamin B in it to say it's actually a different a different product. And uh it's basically been tough to shut down.

SPEAKER_01 9:35

So it's beneficial for the compounders.

SPEAKER_00 9:38

Yeah. Yeah, exactly. So there's a lot of action going on on that side. So all right. So that's now there's another thing, John, that's uh this microdosing trend.

SPEAKER_01 9:49

Aaron Ross Powell You should not be dispensing medical advice, David.

SPEAKER_00 9:52

Aaron Ross Powell I'm not. And just but people are saying, okay, well let's do let's do a micro dose. Now I wish I could do it.

SPEAKER_01 9:58

But but but step back a little bit. What's the difference between a microdose, a normal dose, and a macrodose?

SPEAKER_00 10:04

Aaron Ross Powell The micro dose is very small. So the idea is that you say, hey, maybe and this has been true in other things, like this is some you know, homeopathic uh people try to do this, which is say, I'm just gonna take like a little tiny amount of something and it's gonna have the effect. Now, I actually, John, I love the idea of micro-dosing, and I tried with my, you know, the price of gas has gone up. So I I have a kind of gas guns when I tried to microdose it, and it it stopped on the side of the road. But um so basically, there what I'm suggesting is that there's all sorts of things going on between social media, compounders, et cetera, that it's making this a weird type of a market, um, which also can mean that people aren't necessarily getting the benefits uh the products that they might otherwise.

SPEAKER_01 10:44

I'm not sure that's fair, David. I mean, if you look at the number of clinical categories, so the the clinical data would suggest that in addition to weight loss, which is good, out once you hold that outside of the results, the cardioprotective aspect of this, with heart disease being the leading killer of Americans, I believe, still over cancer and accidental death, uh appear to be very strong. There appear to be um an anti-addictive element to the GLP ones, the the use of those the the the the peptides that may be tied to the to the blood-brain uh sorry, the the brain-gut connection, but we're not quite sure. But there appears to be some very early promising research there. The most interesting stuff I saw recently was TBI, you know, uh brain and concussion. There appears to be some early stuff there. These drugs uh have a category of potentially better effects that are that are growing the more we do research on people who've taken them and can tolerate them. So I I'm I I'm pretty excited about this category. Um and you know, I I would be you you sound a little skeptical of the microdosing, but the uh the the I don't think I've seen a drug introduced for one thing that has had more one indication or clinical impact that have had so many other positive clinical possibilities and indication in such a short period of time.

SPEAKER_00 12:19

Aaron Powell John, the way I look at it is there's all sorts of potential for these products and they're being studied in those areas. Um we don't we don't know where they go, and there's a danger of people just sort of jumping into that. And so I'll just mention some of the things that, you know, as you say, there's many positive things and where it's being looked at. Some of I'll just mention some of the areas where there's been some concerns that have come up. So there's some studies that have flagged some psychiatric issues in terms of depression, anxiety, suicidal ideation. There's concern about people who, let's say, have an eating disorder who may be taking these products. GI, we know there's GI side effects. There's some studies from showing some GI risks.

SPEAKER_01 12:55

There are a subset of people, a pretty substantial subset. I think 50% of the people who try these drugs historically have dropped them within six months, I believe. The it's unclear how much of that was tied to the extraordinary expense or the difficulty in getting access to it. But there's a, you know, there's a fair amount of data that would suggest that for the current chemical formulations of the GLP ones, compounders included, that there are some people just have it's just really hard for them to their their gut to kind of handle that in combination. But I I I think, gosh, you know, for a the scale of the both on label and off-label, where people, to your point, are using it for stuff that may not be initially indicated, morbidly obese weight loss, cardioprotective. That, you know, for for the scale of this, you're not, you know, you're you're not you're not hearing the kinds of things most other weight loss drugs, miracle weight loss drugs, fenfen, they they caused, you know, then they they they did cause weight loss, and they caused a lot of other healthcare problems. This is the first one where it's creating weight loss, substantial and consistent weight loss, but there appear to be a lot of other positives. And then the other thing, David, is that there's an entire wave of GLP ones that are like drugs formulated in different ways to solve for some of the challenges of the current formulation. I think it's pretty exciting. You you you you're sitting there thinking about all the things that could go wrong. I don't know. I I'm I this is one of those things where I think big pharma may have gotten it right in a bigger way than we even realized.

SPEAKER_00 14:34

I think so. You see a lot of activity on the business development side from those companies that have not been involved. So Lily and Novo have been the first ones in, but everybody else is looking to get in and look for some improvements and things. I I have a lot of optimism about it, John. I just think it's uh it's prudent to be careful about it. You know, another area, though, I'll give you on the positive potential side is a topic that we've actually discussed a lot uh on the show related to COVID, and in particular long COVID. Um, as you recall, we've had Zeke Emanuel on really looking to say, well, there's a lot of people, maybe 20 percent of people that had COVID that have some sort of long COVID, and there has not been necessarily that much to do about it. And we talked about this could actually be the big impact of COVID. So it would be interesting about to look at this from a long COVID standpoint, which hasn't been such an exciting field clinically, but as it impacts a lot of people. There is a uh NIH recover initiative, and GLP1s are one of the initial agents uh that they are moving toward um you know enrolling in uh in uh trials and starting actually this summer.

SPEAKER_01 15:43

And and okay, the the the So are are you are you really more of an optimist about these drugs than I than I realized? Perhaps I've mislabeled you as a skeptic.

SPEAKER_00 15:54

What I think that we're qualified to comment on is the business side of it, which I find fascinating, and then also the potential that they have for a lot of different indications and and possibilities. And yes, I do find it very uh interesting and exciting, but I don't I don't want to get ahead of the uh the trials.

SPEAKER_01 16:11

Aaron Ross Powell I think the the thing that's going to be tricky is these are expensive drugs even at the current reduced cost, and the scale of the utilization is still growing, to your point. So it's gonna be a challenge unless people can see a long, a relatively short-term ROI. But I I think I think you know where you can get dramatic and sustained weight loss, I think you're gonna see that, Dave. I mean, I'm I'm I'm uh I'm uh I'm a positive on this one. I I do think that the the the and the thing that's most exciting is you're gonna see because of the success, a lot of research and money go towards seeing whether this similar formulation can be tuned to solve other problems.

SPEAKER_00 16:53

John, let's let's stick for another one more minute on the weight loss side of it. And we hear a lot about the GLP1 rebound rate. Uh there was a study that showed about 60 percent of weight loss that was gained during treatments was regained within a year after stopping. What if what are you seeing there?

SPEAKER_01 17:10

Aaron Powell Well, I I again I think that the the the the the current I think the current approach here has been very pharma-led, which is okay, you know, we've got a great drug, we're gonna charge you a lot of money, it's gonna create a lot of value, be if it's on it forever, not a problem for us, it's a problem for you as an employer, as a as a patient. I think you're starting to see employers um work with uh businesses like my wife's you know food is medicine business, Nourished RX, where you you combine it with a behavioral intervention and teaching people how to cook, how to engage in food in a different way. And with that, I think you could see if you can get that behavior change and teach people how to interact with the food system in their own um the the the I mean the their own urges, that that that could have a a really uh a dramatic positive effect. And the great thing about a GLP1 as an integrated therapeutic is it, you know, you you can you can have an immediate lift often or reduction in in weight loss. No, I'm I'm I I think the tricky thing here is and I may be having a hard time myself, not being too optimistic just because I mean there's I mean I've I've even read that there is some potential cancer reduction possible.

SPEAKER_00 18:33

Yes, that's been well what's happened has been noticed that yes, there have been some um you know some real world data that GLP ones may reduce cancer progression. There's a uh this is actually very current, the 2026 ASCO annual meeting showing GLP1s could reduce cancer progression in lung, breast, colorectol, and liver by a substantial amount, um, and that it correlates in lower mortality risk. So there's a lot of there's a lot of interesting and positive signals uh that are out there. Yes.

SPEAKER_01 19:06

And so where do you land, Dave, as as as a from a business perspective? Do you think these GLP ones are gonna continue to go down in price and become more accessible?

SPEAKER_00 19:18

Yeah, I mean I think that the market is gonna grow overall and that you're gonna see more uses. You're gonna see some tuning of GLP ones, some connection with uh their lifestyle programs. I mean, mentioned we have another guest, a client of ours, Diasome, there uh have a program to help make GLP ones more tolerable so that people actually will stay on them and not have so many, you know, that this is uh early stage.

SPEAKER_01 19:42

But the failure rate or or people just quitting it within a year is not a great answer for something you're saying.

SPEAKER_00 19:50

I know.

SPEAKER_01 19:50

But the thing is, John Trevor Burrus That's a really important investment on their part. Trevor Burrus, Jr.

SPEAKER_00 19:54

No, it is. But you know what it's also interesting. So let's look at these two things, like the GLP1 rebound rate. So people regain 60 percent of the weight. But the thing is, for most diets, most people regain all the weight and sometimes more. And it's also you know, when people win the lottery, they end up poorer. And also, even for drugs like hypertension, uh you know, I think comparably people go off those. And even when people are treating like breast cancer and they have follow-up treatment, people stop taking their drugs. So I am not sure, I know these numbers are cited. I'm not sure the drop-off rate is so much more dramatic for GLP ones than others.

SPEAKER_01 20:28

Aaron Powell Interesting. That's a fair point. So, David, uh lightning round, where are we on Medicare and Medicaid? 50 percent of all the dollars in America, so many people, where are we on the big government programs in terms of coverage? And then let's talk a little bit about where we're going from here.

SPEAKER_00 20:44

So the on the Medicare and Medicaid side, um, of course, a lot of the discussion has been around people that are working age or employed, but most people actually get their their coverage from Medicare and Medicaid. Now, of course, I'll tell you the Biden administration actually had a proposed rule to cover GLP1s for obesity in Medicare. And so, of course, um Trump dumped that and proposed something similar, uh. So it basically tried to have some kind of improvement with this Trump RX program, and now they have- then they came up with this balance model, which was to expand access and Medicare Part D and Medicaid, but the the health insurers didn't go along with it. So now there's this thing, the Medicare GLP1 bridge, which is going to cover these drugs starting in July through the end of 2027, uh, with Medicare footing the bill. Only 13 states are covering in Medicaid, only 13 states cover GLP1s for obesity, and that's actually down from 16 a year ago. So basically the story is Biden set things out in a direction of coverage, Trump undid it and is trying to now redo it.

SPEAKER_01 21:48

I mean, my my read of the current news, Dave, is that they're gonna they're gonna find a way to make it work for Medicare, at least partially because the President keeps talking about it as a positive, which is, you know, uh generally what drives things in the administration. So, Dave, where do we go from here? I mean, this is a I think we're at the beginning of a really interesting phase of of this category of drugs. But but where do you how you're you're the you're the one who knows a lot more about prescription drugs than I do. Trevor Burrus, Jr.

SPEAKER_00 22:17

All right. So I'll give the real big picture the real big picture, John. And thanks for puffing me up, you know. But um, low bar. Low bar. Big picture, John. So if if we look at the public health trends over the past 50 years, they've been bad, right? All the states have gotten worse in terms of the rate of obese and overweight. And actually we are starting to see that change a little bit. So that's actually for the first time, that's that's changing. Then we have these other things where you've got uh cancer, heart disease, which have really been pretty difficult to do anything about, and those may start to have an improvement as well. And then even some of these things we talk about, deaths of despair, psychiatric problems, uh, mental health in general, and maybe those-maybe there is a chance actually to turn the ship. So that's the that's the macro side of it with with GLP ones. Maybe that will work in terms of public health, and maybe it's really gonna pay off from a cost standpoint, regardless of what happens with pricing, which is just one one part of this.

SPEAKER_01 23:15

You're the big maybe here. I'm a more more positive. I I I'm gonna with less information, I want to be more positive here, Dave.

SPEAKER_00 23:24

All right. I thought I was being pretty positive, John. That's about as positive as I get. Maybe I need to macro dose myself so that I would be uh uh be able to give something more positive for next time. Well, what I am gonna say, John, is that that's it for another episode of CareTalk. We've been talking about the current state of the GLP1 drug business, science, policy, and why John is so optimistic, even when his co-host is less so. I'm David Williams, president of Health Business Group.

SPEAKER_01 23:49

And I'm John Driscoll, the chairman of UConn Health. If you like what you heard, or you didn't, or you've got questions, we'd like you all to subscribe on your favorite service.